JP2005312821A - Method for measuring blood flow and longitudinal relaxation time in tissue using high polarization nuclide - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for precisely measuring a blood flow in a tissue using high polarization xenon gas. <P>SOLUTION: In a method of magnetic resonance imaging (MRI), a high polarization nuclide having a polarization ratio for obtaining sufficiently high signal intensity is dissolved within the tissue to detect a magnetic resonance signal, a rising time and an identifying time are estimated from the time transition of the rising section of the identifying section of the signal intensity of chemical shift generated in this magnetic resonance signal, an intra-tissue vertical relaxation time is supposed, and an intra-tissue blood flow is measured. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

    The present invention relates to a method for measuring blood flow volume and longitudinal relaxation time in a tissue using a highly polarized nuclide, and uses a change (chemical shift) in nuclear magnetic resonance frequency of a nuclide dissolved in a living tissue. And a method for measuring the blood flow of an animal and measuring the longitudinal relaxation time (T1) in the tissue.

  The method of measuring the blood flow volume and longitudinal relaxation time in the brain tissue using the highly polarized nuclide of the present invention is an effective technique for examining and monitoring the blood flow of the brain tissue, The same applies to other organs such as lung, heart, liver, kidney, or pathological sites such as tumor or cerebral infarction.

    Radiographic imaging, X-ray CT that captures two-dimensional cross-sectional images, and nuclear magnetic resonance using the difference in transverse relaxation time associated with the nuclear magnetic resonance frequency of water molecules. An image (MRI) method or the like is known. In these imaging methods, a reagent called a contrast agent is used in combination, which generates a signal by itself or attenuates the inherent signal intensity by affecting the surrounding area, thereby causing contrast in the image. There are things to do. In X-ray imaging, it is a good example using such a contrast agent to image the shape of the stomach by oral administration of barium that does not transmit X-rays.

  Positron Emission Tomography (PET) and Single Photon Emission Tomogoraphy (SPECT) are images of signals generated from radioactive contrast media, and the distribution of contrast media is imaged. The Techniques for measuring cerebral blood flow, blood volume, oxygen uptake rate, and oxygen consumption from the temporal transition of signal intensity in such a radiocontrast are well known. A contrast agent used for such an application is generally referred to as a tracer. In the specification of this application, hereinafter, this tracer is also referred to as a contrast agent.

The brain has a physiological structure called the Blood Brain Barier (BBB), and has a mechanism that prevents foreign substances from entering the brain by preventing the passage of large molecular weight molecules. Therefore, depending on the type of contrast agent, only the blood flow in the blood vessel may be measured. In clinical diagnosis, it is well known that the measurement of perfusion flow in the tissue outside the blood vessel is more important. When measuring the cerebral blood flow with a contrast agent, it is preferable to use a contrast agent that passes through the cerebral blood vessel barrier. It is said that. Some radioactive contrast agents containing nuclides such as ¹³³ Xe, ¹⁵ O, and ¹¹ C used in PET and SPECT pass through the brain-vascular barrier. By using such a contrast agent, brain tissue outside the blood vessel can be obtained. The internal perfusion flow can be measured. However, when using radiocontrast media, exposure to patients, laboratory technicians, and doctors is inevitable. Sufficient care is required for the examination, and a blood flow measurement method that does not involve exposure is desired.

Nuclear magnetic resonance tomography (MRI) is a technique that enables tomographic imaging by combining techniques such as nuclear magnetic resonance (NMR), gradient magnetic field, and Fourier transform. There is a possibility to measure. However, currently popular MRI apparatuses are limited to those based on nuclear magnetic resonance (NMR) signals from protons contained in water molecules, and generally provide morphological images based on the distribution of water molecules inside the living body. Only. This depends on the fact that a nuclear magnetic resonance (NMR) signal intensity is weak and can be measured only with a substance having a large number of molecules, and no signal is observed in a minute dose such as a contrast medium. This is because the magnetic resonance phenomenon is a phenomenon based on the Zeeman effect, and its intensity depends on the magnitude (M _p ) of the generated magnetization vector. The following equation (1) shows the magnitude of the magnetization vector.

  γ is the gyromagnetic ratio, n is the nucleon number density in the minute space, and p is the polarization rate.

Considering the case where the system is in thermal equilibrium with the outside, such as protons in water molecules, the polarization rate is calculated from the Boltzmann distribution by the following equation.

γ is the gyromagnetic ratio (2.68 × 10 ⁻⁸ rad / s / T at ¹ H, 0.74 × 10 ⁻⁸ rad / s / T at ¹²⁹ Xe, and B _q is the static magnetic field strength (T ), Κ is Boltzmann's constant (1.381 × 10 ⁻³⁴ J / K), and T is an absolute temperature.

When the polarization rate in ¹ H and 1.5 T at 37 ° C. is calculated, it is about 5 × 10 ⁻⁶ , which is a very small value. Therefore, a nuclear magnetic resonance (NMR) signal cannot be acquired with a contrast agent that can introduce only a very small amount. Therefore, blood flow measurement using a contrast agent such as PET or SPECT is not performed in the examination using the current MRI apparatus.

However, even in an MRI apparatus, as disclosed in Patent Document 1, the local magnetic field-dependent lateral relaxation time (T2 ^* ) of proton atoms is reduced by a magnetic substance-containing contrast agent, for example, a GD-chelate such as Gd-DTPA. There has been proposed a method of measuring cerebral blood flow by changing the signal intensity over time.

  However, since there is a cerebrovascular barrier, there is a problem that a reagent having a large molecular weight such as GD-chelate does not penetrate outside the blood vessel. As described above, in clinical diagnosis, measurement of perfusion flow in a tissue outside the blood vessel is more important, and cerebral blood flow measurement using a contrast agent that does not pass through the cerebral blood vessel barrier is not preferable. Usually, the polarization rate is determined only by the static magnetic field strength and the temperature, but as disclosed in Patent Document 2, the polarization rate of the xenon atom is 10,000 times that of the thermal equilibrium state by an optical pumping method using an alkali metal atom. Using the above method, a method using xenon gas as a contrast agent has been devised.

Highly polarized ¹²⁹ Xe as a highly polarized nuclide is a contrast agent that can pass through the cerebrovascular barrier, and because of its high polarization rate, nuclear magnetic resonance can be observed with a small amount of contrast agent. Several reports have been made on nuclear magnetic resonance imaging using the highly polarized ¹²⁹ Xe gas component. Xenon is fat-soluble and easily dissolves in living tissues. For this reason, it is known that a phenomenon called chemical shift occurs due to a change in the magnetic field environment around the dissolved ¹²⁹ Xe, and shows a nuclear magnetic resonance frequency different from that of the gas component. Using the signal at this chemical shift frequency, there is a possibility that blood flow can be measured from the signal attenuation characteristics, and there is a possibility that oxygen saturation can be measured from the estimation of the longitudinal relaxation time in the tissue. The tissue temperature may be measured from the change.

特表特許公報２００２−５３９８８０ 特表特許公報２００２−５０７４３８ The chemical shift frequency of the nuclide dissolved in the solvent is generally expressed in ppm. When the nuclear magnetic resonance frequency before dissolution in the solvent is represented by F ₀ and the nuclear magnetic resonance frequency after dissolution is represented by F, Chemical shift frequency F _p is expressed by the following equation.

JP Patent Publication 2002-539880 JP Patent Publication 2002-507438

^In one report on chemical shifts in which ¹²⁹ Xe is dissolved in living tissue, a gradient magnetic field is applied in the chest of an experimental animal, slices are selected, and a spectrum is obtained, whereby 192 ppm is adipose tissue, 199 ppm is lung tissue, 210 ppm Is a signal derived from blood. In one report, two peaks were observed in the human brain, and from the time transition of the signal intensity, a signal of 197 ppm was a signal of brain gray matter (a part containing a lot of nerve cells), and a signal of 194 ppm was a brain white matter Presumed to be a signal from (a part containing a lot of nerve fibers). In any report, the grounds for the origin of the signal are uncertain, and it is difficult to say that a certain peak is identified as a signal from which site on the spectrum showing nuclear magnetic resonance.

  In addition, unlike the nuclear magnetic resonance phenomenon of protons, a highly polarized xenon has a characteristic attenuation called cos θ attenuation caused by irradiation with a high-frequency pulse when acquiring a nuclear magnetic resonance (NMR) signal. In other words, there is a phenomenon in which the intensity of the nuclear magnetic resonance (NMR) signal changes by trying to measure the concentration of the contrast agent, and the situation is different from that of a radioactive contrast agent that can be passively observed. When estimating the rise time and the washing time using highly polarized xenon, it is necessary to consider the effect of this cos θ attenuation. In addition, the longitudinal relaxation time in the tissue corresponds to the concept corresponding to the half-life of the radioisotope, but is a time scale equivalent to the washing time, and this influence cannot be ignored when estimating the blood flow.

  When measuring brain tissue blood flow from the time transition of the signal intensity using highly polarized xenon, it is important to calculate from which frequency spectrum. In other words, it is necessary to know in advance which frequency spectrum is from which tissue.

  Further, when using polarized xenon for cerebral blood flow measurement, it is necessary to consider cos θ attenuation in estimating the washout time.

  Furthermore, since the longitudinal relaxation time in the tissue is relatively short and is about the same as the washing time, the handling of the longitudinal relaxation time in the tissue becomes a problem when measuring the blood flow rate.

  The present invention has been made in view of the above-described circumstances, and an object thereof is to provide a method for measuring blood flow in a tissue, particularly in a brain tissue, with high accuracy using a highly polarized xenon gas. It is in.

  The present invention estimates brain tissue blood flow from one chemical shift peak having the maximum value among chemical shift peaks appearing in the vicinity of 200 ppm based on the fact that a plurality of peaks become single in an experimental animal. The object is to provide a method for measuring blood flow in brain tissue.

  That is, in MRI, when a highly polarized nuclide having a polarization rate capable of obtaining a sufficiently large nuclear magnetic resonance (NMR) signal intensity is administered and dissolved in the tissue, the rising edge of the signal intensity of chemical shift or washing out It is intended to provide a method for measuring blood flow in a tissue assuming a longitudinal relaxation time in the tissue by estimating a rise time and a washing time from the time transition of the section.

  Further, the present invention provides a rising interval of signal intensity of chemical shift when a highly polarized nuclide having a polarization rate capable of obtaining a sufficiently large nuclear magnetic resonance (NMR) intensity is administered and dissolved in tissue in MRI. Or, including the method of measuring the longitudinal relaxation time in the tissue assuming the blood flow volume in the tissue by estimating the rise time and the wash time from the temporal transition of the wash out period, these rise time or wash out time In the estimation of the spectral signal intensity by a method including simultaneous estimation of flip angles by a plurality of RF irradiations configured at different repetition times, or by assuming a flip angle, spectral signal intensity attenuation by two RF irradiations A method for estimating the washout time from the above is provided.

As contrast agents for obtaining chemical shifts from living tissue, polarization rates such as optical pumping, dynamic nuclear polarization (DNP) using the overhauser effect, or parahydrogen induced polarization at cryogenic temperatures are used. It is preferable to use a greatly enhanced nuclide ( ³ He, ¹³ C, ¹²⁹ Xe), and such a nuclide is inhaled into the lung by respiration or a solution in which a polarized rare gas is dissolved is directly administered into a blood vessel. It is necessary to be taken into a living tissue by the technique to do.

  The inhalation method to the lung is based on the bolus inhalation method in which the highly polarized nuclide is inhaled for only one breath, or measured from the washing time after the signal is almost steady after continuous administration of the highly polarized nuclide. What can be considered.

  As the measurement site, in the state where no gradient magnetic field is applied, the blood flow rate or the longitudinal relaxation time in the tissue is estimated from the chemical shift of the entire brain, or the xenon spectrum is locally obtained such as the CSI method, the Press method, and the Steam method. A method is conceivable in which the acquisition region of the spectrum is limited by a method.

When highly polarized ¹²⁹ Xe is employed as the highly polarized nuclide, it is known that the frequency of the nuclear magnetic resonance frequency F ₀ in the gas state varies depending on the temperature or the like. Therefore, the value at room temperature (25 ° C.) before inhalation of intake air is adopted as the reference frequency for chemical shift. With respect to this reference frequency, among chemical shifts defined by the equation (3), preferably, a chemical shift peak having a maximum value among a plurality of chemical shift peaks appearing around 200 ppm is specified, and the chemical shift having this maximum value is specified. Estimate blood flow from Desirably, in a small animal, the brain tissue blood flow rate and the longitudinal relaxation time in the tissue are measured using the signal intensity expressed at 195 ± 1 ppm, and in humans, the brain tissue is measured using the signal intensity of 197 ppm. It is intended to measure blood flow.

  Compared to the blood flow measurement method using a magnetic substance-containing contrast agent that has been used in conventional MRI, the blood flow measurement method using xenon gas has a value reflecting the blood flow in the tissue. What is important in clinical findings is not the blood flow in the blood vessel but the blood flow in the tissue, and the blood flow measurement method using xenon gas as a highly polarized nuclide is excellent in this respect.

  Even with PET, a value reflecting the blood flow in the tissue can be measured. However, since it is necessary to use a radioactive substance, xenon gas as a highly polarized nuclide having no radiation can reduce the influence on the measurement target.

  An embodiment of a method for measuring blood flow in brain tissue using the highly polarized xenon of the present invention will be described below with reference to the drawings.

The highly polarized nuclide used in the present invention may be any nuclide as long as the magnetic resonance phenomenon is observed as a contrast agent, but has a non-zero nuclear spin in order to have a nuclear magnetic resonance frequency. Among them, it is necessary to be a nuclide, and among them, the method of highly polarizing to date is known as ³ He, ¹²⁹ , which is known to be highly polarized by an optical pumping method using an alkali metal. It is ¹³ C highly polarized by a technique such as dynamic nuclear polarization (DNP) using Xe or the overhauser effect, or parahydrogen induced polarization at a very low temperature. Regarding ³ He, a technique for directly improving the polarization rate using a 1083 nm laser is also known.

Among these, xenon as a highly polarized nuclide is fat-soluble, easily dissolves in living tissues, and is a rare gas, so it has little interaction with living tissues, so it is useful for measuring blood flow in the brain. Xenon corresponds to the most suitable nuclide. In particular, although it is spin 0, ¹²⁹ Xe, which is a radioisotope, has been used for cerebral blood flow measurement since ancient times. First, a method for generating the highly polarized ¹²⁹ Xe will be described with reference to FIG.

<Method of generating highly polarized ¹²⁹ Xe>
The principle of the optical pumping method, which is the basis of the xenon polarization treatment, causes D1 excitation of valence electrons by irradiating circularly polarized light to vapor-like alkali metal atoms in a static magnetic field. Rubidium (Rb) is generally used as the alkali metal. This excitation returns to the ground state on the order of only a few ms, but at this time, the electron spin magnetic field direction component (m _j ) does not change with a probability of 1/2. By repeating this, polarization of alkali metal atoms proceeds. When this process is performed in a gas of ¹²⁹ Xe, spin exchange occurs due to scattering of alkali metal atoms and ¹²⁹ Xe atoms, and polarization shifts to ¹²⁹ Xe nuclei.

For example, high polarization ¹²⁹ Xe can be generated in the polarization device shown in FIG. This apparatus comprises a gas line 10 through which xenon gas flows, an electromagnet system 12, and a laser system 14 for optical pumping. As the electromagnet system 12, a central magnetic field strength (maximum 100G) is generated. For example, a Helmholtz type electromagnet 16 having a diameter of 34 cm is disposed in the apparatus, and a polarization cell 18 (material: Pyrex or fused quartz, (Diameter 40 mm × length 80 mm). The cell 18 is filled with 1 g of rubidium metal, and warm air supplied from the heater 20 is sent to the upper part of the cell 18 to heat the cell 18 to 70 to 120 ° C. The cell 18 is connected to the gas line 10 and heated to generate rubidium vapor in the gas in the cell 18. The gas line 10 is connected to a vacuum pump (not shown), and before the gas is supplied to the line 10, the inside thereof can be exhausted. The gas supplied to the gas line 10 is three kinds of xenon, nitrogen and helium supplied from the gas cylinders 22, 24 and 26, respectively, and can be arbitrarily mixed manually. As xenon, two kinds of gases, a natural blending ratio ( ¹²⁹ Xe: 26.4%) and a concentrated gas ( ¹²⁹ Xe: 91%) can be used.

The light for optical pumping is circularly polarized light having a wavelength of 794.8 nm and an output of 80 W. As the light source 28, FAP System DUO (a laser light source obtained by attaching a circularly polarized module to a laminated semiconductor laser) can be used. In order to increase the polarization rate, the highly polarized ¹²⁹ Xe is mixed with, for example, 20% of inert nitrogen gas, mixed with xenon gas, sent to the pumping cell 18, heated by the heater 10, and from the light source 28. The light irradiation to the cell 18 is started. The gas pressure at this time is preferably high, but high polarization can be achieved even at 1.3 to 1.6 atmospheres. In this state, if irradiation with circularly polarized light is continued for about 30 minutes, approximately 5 to 10% of highly polarized ¹²⁹ Xe gas can be obtained. This is a polarization rate close to 10,000 times that of the thermal equilibrium state. The highly polarized ¹²⁹ Xe gas is supplied to a gas bag or an ice cell (not shown) through the syringe 30 of the gas line 10.

The polarization rate of the highly polarized ¹²⁹ Xe gas can be measured by a detection system (not shown) based on the fast adiabatic passage method (CW method). A main coil, a transmission coil, and a reception coil that create a main magnetic field for polarization are arranged vertically, and a static magnetic field is applied while applying an oscillating magnetic field having a frequency corresponding to the resonance frequency of 100 gauss of xenon. Sweep slowly. The direction of spin is reversed by resonance, and the nuclear magnetic resonance (NMR) signal at that time is detected by a pickup coil, and the polarization rate can be calculated based on the signal from the sample in a thermal equilibrium state. When applied to experimental animals, signals must be observed with a polarization rate of at least 1%.

Highly polarized ¹²⁹ Xe is extracted from the syringe 30 connected to the extraction gas line 10. In the measurement, after the polarization, the gas extraction gas addition is repeated, and the system can generate the polarization rate of 5% to 10% and the gas volume of 25 cc at intervals of about 7 minutes. As a representative example, a 25 cc generating device for application to experimental animals has been described. However, the highly polarized ¹²⁹ Xe used in this experiment does not depend on such a device, but rather considering human application. It is preferable to use a continuous flow type capable of generating a larger amount of gas or a method of freezing and concentrating a diluent gas (for example, 98% helium gas mixed) with liquid nitrogen that can improve the polarization rate. In the continuous flow type apparatus, the gas is supplied to a gas bag (not shown) and accumulated, and in the technique of freeze concentration, the gas is supplied to an icing cell (not shown) and accumulated in an icing state.

<Spectrum attribution>
In order to clarify the attribution of spectrum in animals inhaled with this highly polarized ¹²⁹ Xe, experiments to block the blood flow to the head other than the brain parenchyma were performed, and the position of the spectrum obtained from the brain tissue was clarified. The following experiment was conducted.

  In mammals, the blood vessels that supply nutrients to the brain are composed of the vertebral arteries (VA) and the common carotid arteries (CCA). It is known that the external carotid arteries (ECA) branched from the internal carotid artery and the pterygopalatine arteries (PPA) account for the majority.

By blocking ECA / PPA, the spectrum of the remaining nuclear magnetic resonance (NMR) signal is considered to be a signal derived from brain tissue. FIG. 2 shows an outline of this experimental example. In this experiment, six male SD rats 32 (320g-460g, n = 6; 3 ECA / PPA blockers, 3 normal cases) were prepared and the spectrum of nuclear magnetic resonance (NMR) signal was confirmed. . Here, for the three SD rats 32, blood flow to the head other than the brain parenchyma was blocked, and the other three SD rats 32 were left untreated. In this experiment, rat 32 mixed halothane (4% at the time of introduction, 1.5% at the time of operation) with a mixed gas of laughing gas and oxygen (70% N ₂ O, 30% O ₂ ). Under anesthesia with anesthesia gas 34, a rat tracheal tube 36 (Atom 8Fr; inner diameter of 3 mm) is inserted into the trachea of rat 32, and a thin tube 38 for administration of xenon is coaxially connected to rat tracheal tube 36. It is inserted in a shape. By inserting the thin tube 38 into the rat tracheal tube 36 in this way, the xenon gas supplied from the syringe pump 40 can be efficiently applied to the lung. At the same time, in the three blood flow blocking animals, the left and right CCA were displayed, and ECA and PPA were tied with a string to block blood flow.

The MRI measurement is performed with a 4.7T Varian MRI measurement apparatus, and utilizes a surface coil 42 that can be tuned to both homemade 3 cm proton-xenon. Wear a fiber optic rectal thermometer (FISO, FTI-10) in the rectum and a pulse oximeter (NONIN 8600V) using near-infrared rays on the hind legs. Body temperature, heart rate, blood oxygen saturation during measurement Is measured to confirm that it is under normal physiological conditions. During the measurement, the depth of anesthesia was maintained by halothane anesthesia (0.5-1%) or α-chloralose (20-40 mg / kg / h was continuously administered from the tail vein). The highly polarized xenon gas is a highly polarized gas (91% enriched enriched ¹²⁹ Xe 80%, N ₂ 20%) prepared by a polarization device using the above-described optical pumping method using an alkali metal, and is a FAP method. The polarization rate obtained by the above is approximately 2-8%.

  The xenon administration line 38 is composed of a tip (PE10; 26 cm), PE50 (70 cm), and 4Fr tracheal tube 36 (30 cm), and is connected to the disposable syringe 40 via a three-way stopcock. The line 38 was inserted into the intubated tracheal tube 36 and its tip was placed in the vicinity of the lung. After each experiment, 25 cc of highly polarized Xe gas was transferred from the pumping cell 18 of the homemade polarization device to a 20 ml disposable syringe 40, and then connected to the line outside the magnet 42, and the syringe 40 was pushed out manually. Was inhaled into the lungs.

  In the measurement, the xenon signal is measured after confirming the position of the rat and shimming at the proton frequency. The transmission / reception frequency of the hard pulse was set to a frequency about 150 ppm away from the gas peak. The measurement frequency width is 30 kHz, 12 kpoints, and the measurement time is 0.4 seconds. The rat is breathing spontaneously, and is drifting around the head of the experimental animal in a state where the gas exhausted from the lungs and the gas leaked without being inhaled by the animal are mixed. A gas drifting around the surface coil 42 is observed. The median of the half width of this gas peak was defined as 0 ppm, and the value of chemical shift was defined from the measurement frequency and bandwidth. The spectrum was displayed after performing convolution integration (equivalent to an increase in bandwidth of 20 Hz) using an exponential function before Fourier transform, and then performing phase correction.

  A typical spectrum obtained from an experimental animal (male SD-Rat, 8W, 320 g) that has not blocked ECA / PPA is shown in FIG. Approximately 5% highly polarized Xe gas is inhaled for 40 seconds, and hard pulse (pulse width 24us, pulse intensity about 10W) for 60 times (about 70 seconds) every 1.25sec from about 3 seconds before the start of inhalation It is the data which applied. FIG. 3 shows the sum of all 60 spectra, with a large peak (main peak) observed at 195.2 ppm, the second largest peak (sub peak) at 189.5 ppm, and 198.3 ppm. , Peak is observed though it is as small as 192.1 ppm. A very wide peak is observed around 210 ppm. FIG. 4 shows the area of the main peak calculated in half width (196.1 ppm-194.8 ppm) and the time transition of the peak area plotted. In each peak, the average value of 30 to 40 seconds is normalized and displayed as 1.

  In order to increase the signal-to-noise ratio, xenon was inhaled over 30 to 40 seconds, and then a pulse was applied only once several seconds later to observe the spectrum. FIG. 5A shows a spectrum obtained from a normal rat. This is a sum of several data performed in each rat. Normalization is performed with the maximum value of the main peak as 1.

  In Rat # 12 and Rat # 16, as in Rat # 21, a main peak was observed around 195 ppm, and a sub peak was observed around 190 ppm. The position of the main peak was 194.8 ± 0.2 ppm, and the position of the sub peak was 189.2 ± 0.2 ppm.

  The peaks near 199 ppm and 192 ppm located on both sides of the main peak are not clear, but the spectrum width broadens in the lower part, suggesting that a peak similar to Rat # 21 exists.

  FIG. 5 (B) shows the spectrum obtained from the rat that blocked PPA / ECA. In these three cases, almost no subpeak near 190 ppm is observed in any rat. Further, it can be read that the peaks near 199 ppm and 192 ppm located on both sides of the main peak are not observed with no band broadening. The position of the main peak is 195.0 ± 0.3 ppm, and it is 194.9 ± 0.3 ppm when considered in combination with normal rats.

  Rat # 15 and Rat # 16 were intravenously injected with Evans Blue after the experiment, and staining near the scalp was confirmed, whereas in the blood vessel-blocked animal (Rat # 15), it was not stained In normal animals (Rat # 16), it was stained blue. From this, it is understood that the supply of blood to the temporal muscle near the scalp is lost due to the blockage of PPA / ECA.

Considering the above experimental results, the spectrum obtained from brain tissue among the five peaks shown in the vicinity of 200 ppm in FIG. 3 is only the peak existing at 194.9 ± 0.3 ppm, and the others are muscle and It is understood that it is a peak other than brain tissue such as skin. By analogy with this, even in humans, the chemical shift obtained from brain tissue is only the one with the maximum value among the chemical shift peaks appearing around 200 ppm, and information on brain tissue can be obtained from other peaks. It is considered impossible. Therefore, when the highly polarized nuclide is administered and dissolved in the tissue, the rise time and decay time are estimated from the rise time of the chemical shift signal intensity or the time transition of the wash out time. Assuming relaxation time, the method of measuring the blood flow in the tissue should be applied only to the one having the maximum value among the plurality of chemical shift peaks appearing around 200 ppm. ^In the case of Rat, where ¹²⁹ Xe is administered by pulmonary inhalation, it is particularly desirable to utilize the peak present at 194.81 ± 0.3 ppm. However, the reference frequency used in this experiment is a mixture of the gas exhausted from the lungs and the gas leaked without being inhaled by the animal, using the gas drifting in the head of the experimental animal. Yes. It has been found that the nuclear magnetic resonance frequency of ¹²⁹ Xe at room temperature can vary by approximately 1 ppm from the experimental reference frequency, and the position of the chemical shift measured from brain tissue is greater than the standard deviation, It should be construed that it is located at 195 ± 1 ppm.

  Hereinafter, a method for measuring the longitudinal relaxation time in the tissue and the blood flow in the tissue from the peak of the chemical shift will be specifically described.

<Separation of cos θ attenuation>
Unlike the proton nuclear magnetic resonance phenomenon, in the highly polarized xenon, there is a specific attenuation called cos θ attenuation due to irradiation of a high-frequency pulse when acquiring a nuclear magnetic resonance (NMR) signal. The cos θ attenuation depends on the flip angle that depends on the intensity of the irradiated pulse. The relationship between the pulse intensity and the flip angle depends on the electromagnetic impedance determined by the shape and composition of the target.If the target is the same, there is an almost constant relationship. Different.

As shown in FIG. 4, the nuclear magnetic resonance (NMR) signal from the polarized xenon gradually decreases after the gas supply is completed. Is basically the attenuation depending on the tissue longitudinal relaxation time T ₁ and the blood flow F, here, simply be represented by the decay time τ of the attenuation characteristic. In highly polarized xenon, a specific attenuation called cos θ attenuation due to irradiation of a high frequency pulse when acquiring a nuclear magnetic resonance (NMR) signal is added.

When a plurality of pulses are applied at certain time intervals, that is, every TR time, and the amount of magnetization after the end of gas supply is M _p , the first, second, third. . . The signal intensities I ₁ , I ₂ , I ₃ . . . I _n is proportional to sin component of the initial magnetization M _p and flip angle theta, expressed by the following equation.

In the above formula (7), I ₁ , I ₂ , I ₃ . . . I _n can be measured, TR is a predetermined time interval. Therefore, I ₁ , I ₂ , I ₃ . . . From measurement data of the I _n, it is necessary to find a unknowns τ and theta.

When TR or θ is equal, τ and θ cannot be obtained separately no matter how the above equation is modified. In order to obtain τ and θ separately, it is necessary to obtain a plurality of data by varying TR or θ. For example, it is assumed that the relationship between the flip angle and the pulse intensity is known in advance, and two kinds of pulses of θ and 2θ are applied three times in the order of θ−2θ−θ. The signal strengths I ₁ , I ₂ , I ₃ . . . I _n is is expressed by the following equation.

In this case, if the above equation is modified,

And I ₁ , I ₂ , I ₃ . . . Than I _n, it is possible to determine the theta, if theta is determined, naturally, tau also determined. Alternatively, assume that the interval between three pulses is (2TR-TR).

In this case, if the above equation is modified,

And I ₁ , I ₂ , I ₃ . . . Than I _n, it is possible to determine the tau, if tau is determined, it obtained also natural and theta. In both cases, the method of estimating τ and θ with three pulses has been described. However, it is possible to estimate τ and θ with a technique that combines different flip angles or different repetition times, and is more accurate. High measurement is possible.

As a modification of the method for changing the pulse interval, the following method can also be applied. FIG. 6 shows a schematic diagram of pulse application in a method in which two pulses are applied to a section where the signal intensity is attenuated. The intensity S ₁ of the signal from the first RF pulse is

It is represented by α indicates the detection sensitivity of the detection system, M _p indicates the amount of magnetization when the first pulse is applied, and θ indicates the flip angle by the RF pulse. The magnetization here is as described above.

γ is the gyromagnetic ratio, n is the nucleon number density in the minute space, and p is the polarization rate. Subsequent magnetization draws a different decreasing curve under the influence of cos θ attenuation of the first pulse. Waiting for the gap time TR, giving a second pulse, the signal strength at that time is

Can be represented. From these equations,

  Is obtained.

  It can be seen that the value of τ can be obtained without evaluating the flip angle if the measured values of different TR times are obtained with the applied RF pulse constant and the flip angle constant. In this measurement, since it is not necessary to obtain the flip angle, the evaluation error of the flip angle does not affect the measurement value. Like a surface coil, there is an advantage that it can be used for a signal with high detection sensitivity but poor RF magnetic field uniformity. FIG. 7 shows data obtained by actually measuring the relationship between the decay time of xenon and the flip angle.

This data was measured after ¹²⁹ Xe was inhaled into the lungs of a laboratory animal over 40 seconds, and measured at 4 points of 4, 8, 12, 16 seconds as TR. . From the approximate straight line 40 in FIG. 6, τ is found to be 15.5 ± 1.18 sec and the flip angle θ is found to be 17.97 ± 7.7 degrees.

  The above method is a method for obtaining the attenuation time and the flip angle from the attenuation characteristics when the flip angle is not obtained, but generally, if the applied power is the same under the same experimental conditions, it is generally omitted. It is expected that the same flip angle is obtained, and if the flip angle is measured in advance, the flip angle can be assumed. In this case, in Equation 3, θ can be assumed, so τ can be calculated from two pulses. In general, such a method can be used to reduce the measurement time.

<Relationship between tissue blood flow and decay time 1 (Kety and Schmidt method)>
A method for obtaining the blood flow volume in the tissue and the longitudinal relaxation time in the tissue from the decay time τ thus obtained will be described.

  A calculation method using this decay time is a method similar to PET. Unlike contrast agents containing magnetic substances, which are conventionally used in MRI, xenon gas passes through the cerebral blood vessel barrier, so it is possible to evaluate the blood flow in the tissue, not the blood flow in the blood vessel. Yes, clinical significance is great.

In general, the blood flow measurement method described as the Kety and Schmidt method will be described first. The rare gas is carried by the arterial blood through the lungs to the brain and diffuses through the capillaries to the brain tissue. The blood that has perfused the tissue returns to the vein along with the noble gas. At this time, Fick's principle that the time change rate of the amount _Qbr of rare gas transferred to the brain tissue is expressed by the balance between the input amount (supply from the artery) and the discharge amount (washing out into the vein). It became.

Here, C _a (t) and C _v (t) are the concentrations of rare gases in arterial blood and venous blood, respectively, and F is the blood flow rate flowing in unit time. Here, when Henry's law is established in the relationship between the rare gas concentration and the partial pressure, the partial pressure in the brain tissue is P _br , the partial pressure in the blood is P _bl, and the concentration in the brain tissue is C _br, when representing the concentration in the blood and _{C bl} following equation hold true.

Here, K is a constant, and α is a Bunsen inhalation rate or Ostwald solubility coefficient. In steady state, the partial pressures of arterial blood, venous blood, and noble gases in brain tissue are considered to be equal.

The relationship holds. However, λ is a coefficient expressed by (α _br / α _bl ) in the above equation, and is a coefficient generally known as a distribution coefficient. The value obtained by integrating the equation (22) with time indicates the amount of rare gas transferred to the brain tissue, which is the product of the brain tissue concentration in the steady state and the brain tissue volume W expressed by the equation (26). The following equation holds true for the value to be transferred.

  Is calculated, the cerebral tissue blood flow can be measured. FIG. 8 is a representative example of the concentration curves of arterial and venous noble gases, and shows an example in which a sample from blood is measured.

In this FIG.

Considering the example of highly polarized xenon, the frequency of the polarized xenon spectrum differs between brain tissue and blood. Therefore, the temporal change in the spectrum of arterial blood near 210 ppm is C _a (t), and the brain near 195 ppm Using the fact that the time change of the spectrum from the tissue corresponds to C _v (t), blood flow can be measured based on the above equation (28). At this time, since the spectrum intensities are different from each other, it is necessary to multiply by a coefficient. However, since this coefficient is not a value that differs among examinees, it is possible to obtain the coefficient in advance by calibration with PET or the like.

<Relationship 2 between tissue blood flow and decay time (compartment model method)>
Next, a blood flow measuring method generally described as a compartment model method will be described. This method assumes an exponential decay curve by solving a differential equation in which the amount of change in contrast agent concentration is proportional to the concentration at that time. The differential equation is expressed by the following equation.

It becomes. In order to consider the value of k in this formula, in several washings from the blood vessel, the contrast agent in the blood vessel is continuously washed out in a state where the contrast agent is uniformly diffused in the tissue and the blood vessel, and then instantaneously. Let us consider the change in concentration, assuming that the concentration becomes uniform by diffusion. As shown in FIG. 9 (a), the blood vessel volume is V, the brain tissue volume is W, and after the contrast medium in the blood vessel is washed out, the brain tissue as shown in FIGS. 9 (b) to 9 (e). Assuming that the operation in which the contrast agent in the blood instantly spreads in the blood vessel is repeated n times, the amount Q _br of the contrast agent in the brain tissue after n times is expressed by the following equation.

Assuming that the time for one turnover is t ₀ , the contrast agent amount Q _br after t time is

Here, F is the blood volume, and the blood flow f is considered as F / W.

Therefore, in the compartment model, the blood flow rate is calculated by the following equation from the slope k of fitting the signal attenuation characteristic of the washing section with an exponential function.

<Application of the compartment model method to ¹²⁹ Xe>
In radioactive contrast media, the decay time due to the decay of radiation is sufficiently longer than the washout time, and the signal decay characteristics are sufficient considering only the washout time due to blood flow, but in vivo longitudinal relaxation of highly polarized ¹²⁹ Xe Since the time (T1 _{, tissue} ) is short, the following equation must be considered in consideration of this effect.

k is a proportionality constant described in (29), and has the relationship of the decay time τ and τ = 1 / k described in the equations (17), (20), and (21). f is the blood flow volume (ml blood / 100 g tissue / s), T _{1, tissue} is the longitudinal relaxation time of xenon in the _tissue , λ is the partition constant of xenon between blood and tissue, It is a value calculated from the solubility ratio.

  From the above, it can be seen that the decay time is determined from the blood flow in the brain tissue, the in vivo longitudinal relaxation time, and the xenon partition constant between blood and tissue. The xenon distribution constant λ between blood and tissue is a value that does not change over time and is considered to be a constant value regardless of the individual, but the blood flow in the brain tissue varies depending on the location and medical condition. It is known that the longitudinal relaxation time varies depending on the oxygen partial pressure or the like.

<Separation of cerebral blood flow and in vivo longitudinal relaxation time by model animals>
In actual measurement, it is preferable to obtain the cerebral blood flow rate or the in vivo longitudinal relaxation time by obtaining the decay time. In general, the longitudinal relaxation time in vivo is considered to be almost constant. If a plurality of samples are measured in advance, the cerebral blood flow is calculated from the decay time assuming the longitudinal relaxation time in vivo. It is possible.

  Alternatively, the in vivo longitudinal relaxation time can be measured based on the blood flow rate by measuring the blood flow rate by a method different from the Xe decay time measurement method (for example, PET or the like). It is suggested that the longitudinal relaxation time in the body may change depending on the oxygen saturation in the tissue, and it is a meaningful measurement method that the longitudinal relaxation time in the body can be measured. Here, in order to calculate the cerebral blood flow from the decay time assuming the longitudinal relaxation time in vivo, the relationship between the relaxation time and blood flow can be determined by changing the blood flow with a drug or the like using a model animal. The result of conducting an experiment is shown.

As shown in FIG. 2, confirmation was performed using two male SD rats. Under anesthesia in which halothane (4% at the time of introduction, 1.5% at the time of surgery) is mixed with a mixed gas of laughing gas and oxygen (70% N ₂ O, 30% O ² ), the tracheal tube 36 (Atom 8Fr The inner diameter is 3 mm). A laser Doppler blood flow meter (not shown) was fixed to the head in order to measure the blood flow in the brain. The MRI measurement is performed with a 4.7T Varian MRI measurement apparatus, and utilizes a surface coil 42 that can be tuned to both homemade 3 cm proton-xenon. Wear a fiber optic rectal thermometer in the rectum and a pulse oximeter using near-infrared light on the hind legs to measure body temperature, heart rate and blood oxygen saturation during measurement, and be in normal physiological conditions Have confirmed. During the measurement, α-chloralose (20-40 mg / kg / h) was continuously administered from the tail vein to maintain the depth of anesthesia.

The highly polarized xenon gas is a highly polarized gas (91% enriched enriched ¹²⁹ Xe: 80%, N, produced by the polarization device using the optical pumping method using the alkali metal described above with reference to FIG. ₂ : 20%), and the polarization rate determined by the FAP method is approximately 2-8%.

  The xenon administration line consists of a tip (PE10; 26 cm), PE50 (70 cm), and 4Fr tracheal tube (30 cm), and is connected to a disposable syringe via a three-way stopcock. This line was inserted inside the intubated tracheal tube and its tip was placed in the very vicinity of the lung. After each experiment, 25cc of highly polarized Xe gas was transferred from the pumping cell of the homemade polarization device to a 20ml disposable syringe, then connected to the line outside the magnet and manually pushed into the lungs Inhale.

  In the measurement, the xenon signal is measured after confirming the position of the rat and shimming at the proton frequency. The transmission / reception frequency of the hard pulse was set to a frequency about 150 ppm away from the gas peak. The measurement frequency width is 30 kHz, 12 kpoints, and the measurement time is 0.4 seconds. The spectrum was displayed after performing convolution integration (equivalent to an increase in bandwidth of 20 Hz) by exponential function before Fourier transform, and then performing phase correction.

In order to measure the decay time of xenon, after a high-polarized ¹²⁹ Xe gas is forcibly sent over 40 seconds, as shown in FIG. 6, a pulse is applied twice in the interval where the signal intensity is attenuated. Measurement was performed. The measurement gap time TR was 4, 8, 12, 16 seconds. After this measurement, Diamox (20 mg / kg) was administered from the tail vein of the rat to increase the blood flow. The blood flow is increased approximately 30% by administration of this medicine. FIGS. 10A and 10B show an estimated straight line of the decay time obtained by this method. FIG. 10A shows attenuation characteristics when the blood flow rate is not increased, and the attenuation time is 17.4 seconds. FIG. 10 (a) shows the attenuation characteristics when the blood flow increased by 30% by administration of Diamox, and the attenuation time was 15.1 seconds.

When plotting with the horizontal axis 1 / τ according to the equation (36), the slope of the graph corresponds to f / λ, and the y-intercept of x = 0 corresponds to 1 / T _{1, tissue} . FIG. 11 shows an actually plotted diagram. From FIG. 11, 1 / T _{1, tissue} is 37 seconds, and f / λ is 0.0239. If the weight of the brain parenchyma is 2 g and λ is 1.015, the blood flow is calculated as 73 ml / 100 g / min.

In Expression (36), assuming that T _{1 and tissue} are 37 seconds, f is derived. On the other hand, if f / λ is assumed to be 0.024, T1 _{, tissue} is derived.

<Highly polarized ¹²⁹ Xe spectrum in humans>
The following experiment was conducted to measure the spectrum from the brain in volunteers who inhaled this highly polarized ¹²⁹ Xe from the lungs.

In this experiment, the spectrum of the nuclear magnetic resonance (NMR) signal was confirmed by two subjects. The subject wore a mask for gas suction. Highly polarized ¹²⁹ Xe is supplied in a state of about 500 cc in a 1 liter plastic bag (Tedora bag). This tedora bag is connected to the mask with a three-way stopcock open. At the start of measurement, the subject himself opens and closes the three-way cock, sucks the highly polarized ¹²⁹ Xe, holds the breath for 30 seconds, and holds the gas in the lungs. The highly polarized xenon gas is a highly polarized gas (91% enriched enriched ¹²⁹ Xe: 80%, N ₂ : 20%) prepared by a polarization device using the above-described optical pumping method using an alkali metal. The polarization rate determined by the FAP method is approximately 0.5 to 1%.

  MRI measurement is performed with a 1.5T GE MRI measurement device, and a specially prepared xenon single-tuned 8-element birdcage coil is used.

The measurement unit uses the one built in the GE MRI measurement device, and after the position of the human head is confirmed and shimmed at the proton frequency by the body coil in this measurement unit, the xenon signal is measured. . The transmission / reception frequency of the hard pulse was set to a frequency about 100 ppm away from the gas peak. The measurement frequency width is about 8 kHz, 2 kpoints, and the measurement time is 0.25 seconds. Highly polarized ¹²⁹ Xe gas leaked during inhalation was observed, the median value of the half-value width of this gas peak was defined as 0 ppm, and the chemical shift value was defined from the measurement frequency and bandwidth. The spectrum was displayed after performing convolution integration (equivalent to an increase in bandwidth of 30 Hz) by an exponential function before Fourier transform, and then performing phase correction.

  A typical spectrum obtained from a human is shown in FIG. FIG. 12 shows that approximately 0.5% of highly polarized Xe gas is inhaled for about 5 seconds, and after inhalation, breathing is stopped for 23 times (about 92 seconds) every 4 seconds. Data obtained by applying an angle of about 45 degrees. FIG. 12 shows the sum of all 23 spectrums. A large peak (main peak) is observed at 197.1 ppm, the second largest peak (sub-peak) is present at 194.1 ppm, and 191.3 ppm. The third largest peak (second subpeak) is observed. FIG. 13 shows an enlargement of the vicinity of 200 ppm of the spectrum measured three times from two subjects. It can be seen that three spectra are observed in any spectrum.

<Attribution of highly polarized ¹²⁹ Xe spectrum in humans>
In order to confirm the attribution of the three spectra, an experiment was conducted in which carbon dioxide was inhaled simultaneously when xenon was inhaled. It is known that blood flow increases by inhaling carbon dioxide gas. The increase in blood flow is particularly noticeable in brain tissue, and the rate of increase is small in portions other than brain tissue. If each peak is a signal component derived from brain tissue such as gray matter and white matter, the signal intensity ratio should be the same because both have the same signal rise. For components other than brain tissue, the signal intensity ratio is expected to change. Carbon dioxide gas was supplied at a flow rate of 500 cc / min by placing a thin tube near the mask. Kohenkyoku ¹²⁹ begin inhalation of carbon dioxide gas from 1 minute before inhalation of ^Xe gas, when Kohenkyoku ^{129 Xe} gas inhalation, can be expected to blood flow is increased about 20%.

  FIG. 14 and FIG. 15 plot the area of the peak and the time transition of the peak area by calculating the area with the half width of the main peak and the sub peak at the normal time when carbon dioxide gas is not supplied and when the gas is inhaled. The second sub-peak near 191 ppm is not shown here because it has a low signal intensity and is difficult to distinguish from a noise component. FIG. 16 is a graph in which (main peak area) / (sub peak area) is calculated at each measurement point and the time transition is plotted. It can be seen that the signal intensity ratio increases when carbon dioxide is inhaled. This experimental result is a result which suggests that a subpeak originates in components other than brain tissue.

In consideration of the above experimental results, in humans, the spectrum obtained from brain tissue out of the peaks near 200 ppm in FIG. 12 is a peak present at 197 ppm, and the others are other than brain tissues such as muscle and skin. There is a high possibility that it is a peak. By analogy with this, even in humans, the chemical shift obtained from brain tissue is only the one with the maximum value among the chemical shift peaks appearing around 200 ppm, and it is not possible to obtain information on brain tissue from other peaks. It is considered impossible. Therefore, when the hyperpolarized nuclide is administered and dissolved in the tissue, the rise time and decay time are estimated from the rise time of the chemical shift signal intensity or the time transition of the wash out time. Assuming relaxation time, the method of measuring the blood flow in the tissue should be applied only to the one having the maximum value among a plurality of chemical shift peaks appearing around 200 ppm. ^In humans, where ¹²⁹ Xe is administered by pulmonary inhalation, the peak present at 197 ± 1 ppm is particularly desirable.

The method for measuring the blood flow in the tissue and the longitudinal relaxation time in the tissue from the attenuation characteristics of the highly polarized ¹²⁹ Xe as the highly polarized nuclide has been described above. In the embodiment, the one based on the spectrum obtained from the whole brain is exemplified, but generally known methods such as the CSI method, the Press method, and the Steam method are used to limit the position where the spectrum is acquired by applying a gradient magnetic field. If the time change of the spectrum of the limited position is acquired using, it is possible to measure the blood flow volume in the tissue and the longitudinal relaxation time in the tissue at the limited position.

It is the schematic which shows the apparatus which produces | generates the highly polarized xenon applied to the method of measuring the blood flow rate in a brain tissue using the highly polarized xenon of this invention. It is the schematic which shows the experimental example of the method of measuring the blood flow rate in a brain tissue using the highly polarized xenon of this invention. It is a graph which shows the typical spectrum obtained from the experimental animal which has not interrupted | blocked ECA / PPA in the experiment example shown in FIG. It is a graph of the time displacement shown by spectrum normalization shown in FIG. 3 is a graph showing a spectrum obtained from a normal rat in the experimental example shown in FIG. 2 and a graph showing a spectrum obtained from a rat that has blocked PPA / ECA. It is a graph which shows the method of applying a pulse twice to the area where signal strength attenuates in the method of measuring the blood flow volume in the brain tissue using the highly polarized xenon of this invention. It is the graph which measured the relationship between the decay time of xenon and flip angle in the method of measuring the blood flow volume in brain tissue using the highly polarized xenon of this invention. It is a graph which shows the density | concentration curve of the rare gas of an artery and vein which shows that the brain tissue blood flow rate can be measured in the method of measuring the blood flow amount in brain tissue using the highly polarized xenon of this invention. (A)-(e) is a schematic diagram for demonstrating the model which the contrast agent in brain tissue spreads in the blood vessel in the method of measuring the blood flow rate in brain tissue using the highly polarized xenon of this invention. is there. (A) And (b) shows the estimated straight line of the decay time when the blood flow rate is not increased and when the blood flow rate is increased, which is obtained from the experimental animal. It is the data which shows the relationship between the blood flow rate calculated | required from the experimental animal, and a proportionality constant. It is a graph which shows the typical spectrum obtained from the human in the experiment example. (A), (b) and (c) is a graph which shows the typical spectrum obtained from the human in each experimental example. (A) And (b) is a graph which shows the relationship of the elapsed time at the time of normal time and the time of carbon dioxide inhalation, and the NMR signal from a human brain in a human experiment example. (A) And (b) is a graph which shows the relationship of the elapsed time at the time of normal time and the time of carbon dioxide inhalation, and the NMR signal from a human brain in a human experiment example. (A) And (b) is a graph which shows the relationship between the elapsed time and peak ratio in the said experimental example of the human at the time of normal time and the time of carbon dioxide suction.

Explanation of symbols

  10. . . Gas line, 12. . . Electromagnet system, 14. . . Laser system, 18. . . Polarized cell, 28. . . Laser light source, 32. . . Laboratory rat, 34. . . Anesthetic gas, 36. . . Tracheal tube

Claims (11)

    In nuclear magnetic resonance tomography (MRI), a highly polarized nuclide having a sufficiently high signal intensity is dissolved in tissue to detect a nuclear magnetic resonance signal, and a chemical generated in the nuclear magnetic resonance signal. A method of measuring a blood flow volume in a tissue by estimating a rise time and a wash time from a rise period of a signal strength of shift or a temporal transition of a wash section, assuming a longitudinal relaxation time in the tissue, and measuring the blood flow in the tissue.     In the nuclear magnetic resonance imaging (MRI) method, a nuclear magnetic resonance signal is detected by dissolving it in a highly polarized nuclide tissue having a polarization rate that provides a sufficiently large signal intensity, and the chemical shift that occurs in the nuclear magnetic resonance signal is detected. A method of estimating a rise time and a wash time from a rise time of a signal intensity or a temporal transition of a wash section, and measuring a longitudinal relaxation time in a tissue based on a blood flow in the tissue measured in advance.     The method according to claim 1 or 2, wherein the flip angle is estimated by a plurality of RF irradiations configured with different repetition times in the estimation of the rise time or the washing time.     The estimation of the rise time or the washout time assumes a flip angle, and the washout time is estimated from the attenuation of the spectral signal intensity of the chemical shift caused by two RF irradiations. The method of claim 2, 3. The method according to claim 1 or 2, wherein the highly polarized ¹²⁹ Xe is dissolved in the tissue by adopting a bolus inhalation method in which ¹²⁹ Xe is inhaled into the lung for only one breath as the highly polarized nuclide. ¹²⁹ Xe is continuously administered as the highly polarized nuclide to dissolve the highly polarized ¹²⁹ Xe in the tissue, and the blood flow volume in the tissue is determined from the washing time after the nuclear magnetic resonance signal is almost in a steady state. Alternatively, the method according to claim 1 or 2, wherein the longitudinal relaxation time in the tissue is measured.     3. The method according to claim 1, wherein the blood flow rate or the longitudinal relaxation time in the tissue is estimated from a chemical shift of the entire brain.     The method according to claim 1 or 2, wherein a xenon spectrum is locally detected from the chemical shift to localize an acquisition region of the spectrum. ¹²⁹ Xe is adopted as the highly polarized nuclide, and the brain tissue blood flow rate and the longitudinal relaxation time in the tissue are measured from one chemical shift peak having the maximum value among the chemical shift peaks appearing around 200 ppm as the chemical shift. The method of claim 1 or claim 2 characterized in that.     The method according to claim 9, wherein the brain tissue blood flow rate and the longitudinal relaxation time in the tissue are measured in an animal using the signal intensity expressed at 195 ± 1 ppm in the spectrum.     10. The method according to claim 9, wherein the human blood flow is measured using a signal intensity of 197 ± 1 ppm in the human spectrum.

Images