JP2013255586A - Method for operating mri apparatus in imaging cerebral blood flow - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for operating an MRI apparatus which utilizes O-17 water and has high time resolution in imaging a cerebral blood flow.SOLUTION: A method for operating an MRI apparatus includes: a step of obtaining a signal value derived from O-17 water in the cerebral blood flow of a subject by using a Balanced SSFP method as an image pickup sequence; a step of obtaining a change in time of signal value by repeating the step of obtaining a signal value a plurality times; a step of obtaining a time-concentration curve of O-17 water from the change in time of signal value on the basis of the previously obtained relation between the signal value and the concentration value of O-17 water; a step of obtaining a cerebral blood flow (CBF) and/or a cerebral blood volume (CBV) from the time-concentration curve; and a step of forming a map of CBF and/or CBV by integrating the CBF and/or CBV obtained for each of positions of an image pickup matrix.

Description

  The present invention relates to a method for operating an MRI apparatus in imaging of cerebral blood flow.

  Stroke is a disease in which brain tissue is killed by cerebrovascular obstruction or failure, and is the third leading cause of death among Japanese people. Particularly in an aging society, sequelae, rehabilitation, and nursing care are major social problems, but accurate cerebral blood flow tests are necessary for appropriate prevention and acute treatment.

  There are various methods for cerebral blood flow examination, but there is no method that is non-invasive, has a low patient burden, is excellent in quantitative properties, and can be easily used in general clinical practice. Nuclear medicine examinations such as PET and SPECT are exposed to radiation, have a long examination time, and have a low spatial resolution. PET is excellent in quantitativeness and is a standard for cerebral blood flow test, but the facilities that can be used are limited. On the other hand, CT / MRI perfusion images are clinically applied as a simple method because they can be imaged and analyzed in many facilities in a short time, but intravenous administration of a contrast agent such as gadolinium (Gd) chelate is essential, There are restrictions on the risk of side effects of contrast agents, renal dysfunction, etc., such as cardiopulmonary arrest due to contrast agent allergy. Further, the contrast agent is an intravascular tracer and behaves differently from a diffusive tracer such as PET. Furthermore, CT perfusion images have drawbacks such as radiation exposure and a narrow imaging range, and MRI perfusion images have low quantitativeness. As a method that does not use a contrast agent, MRI also has an ASL (arterial spin labeling) method in which blood is labeled with RF, but there are problems of label duration and transit time, and sufficient quantitativeness cannot be expected.

Under such circumstances, it has been proposed to use ¹⁷ O, which is a non-radioactive isotope (stable isotope) of oxygen, as a probe for MRI measurement. ^{Although 17} O exists in nature only at 0.037%, ¹⁷ O-labeled water molecules (H ₂ ¹⁷ O, hereinafter referred to as “O-17 water”) have a T2 shortening effect based on cross relaxation (J bond). If the concentration is sufficient, it is possible to detect a signal change by MRI. O-17 water is a stable isotope, so there is no radiation exposure, and since it is water, there is no allergic reaction. The present inventors conduct basic experiments by 3 Tesla MRI using beagle dogs, and visualize the water molecular dynamics in cerebrospinal fluid under intravenous administration of 10% O-17 water using an original analysis program. It was the first success in the world. In addition, by using a high-contrast imaging method devised uniquely, we succeeded in capturing the changes in the brain parenchyma corresponding to cerebral blood flow for the first time.

In addition, (Patent Document 1) discloses a drug for analyzing the water transport function of membrane protein in a biological tissue, and the abundance of one or both of ¹⁷ O water molecule and ¹⁸ O water molecule in the drug for analysis. However, there is disclosed a drug for analyzing water transport function, characterized in that it is greater than the abundance in natural water.

Further, (Patent Document 2) is a biotolerable aqueous solution in which the active ingredient is H ₂ ¹⁷ O, and the T2 relaxation degree of the aqueous solution is 0.1 s ⁻¹ atom% ⁻¹ or more. A nuclear magnetic resonance diagnostic agent is disclosed.

  However, O-17 water has not been used for cerebral blood flow examination by MRI. The above (Patent Document 2) suggests an application to a cerebral blood flow test. However, a spin echo method T2 enhancement method, various T1ρ enhancement methods, and the like can be selected for a sequence used for imaging. However, it is only described as a general examination method, and an imaging sequence and imaging conditions that can actually perform a cerebral blood flow examination are not disclosed. There is no attempt to use O-17 water for cerebral blood flow examination by MRI both in Japan and overseas, and it is considered very promising as a novel cerebral blood flow examination that can achieve both low invasiveness and quantitativeness. An imaging method with high time resolution is required for measurement, and development is not easy.

JP 2008-239666 A JP 2003-102698 A (Claim 11)

  Therefore, in view of the above-described conventional situation, an object of the present invention is to provide an operation method of an MRI apparatus having high time resolution in imaging of cerebral blood flow using O-17 water. It is another object of the present invention to provide a method for operating an MRI apparatus that can observe signal changes even when the O-17 water concentration in the blood vessel is low.

  As a result of intensive studies by the present inventors, an imaging sequence called “Balanced SSFP method” is adopted when imaging a subject administered with O-17 water, and the method is further used for cerebral blood flow measurement. The present invention has been completed by finding that the above problem can be solved by tuning to a low spatial resolution and increasing the temporal resolution. That is, the present invention includes the following inventions.

(1) Using the Balanced SSFP method as an imaging sequence, obtaining a signal value derived from O-17 water in the subject's cerebral blood flow;
Repeating the step of obtaining the signal value a plurality of times to obtain a time change of the signal value;
Obtaining a time concentration curve of O-17 water from the time change of the signal value based on the relationship between the signal value obtained in advance and the O-17 water concentration value;
Determining cerebral blood flow (CBF) and / or cerebral blood volume (CBV) from the time concentration curve;
Integrating the cerebral blood flow (CBF) and / or cerebral blood volume (CBV) obtained for each position of the imaging matrix to create a map of cerebral blood flow (CBF) and / or cerebral blood volume (CBV) And a method of operating the MRI apparatus in imaging cerebral blood flow.
(2) The operation method of the MRI apparatus according to (1), wherein the imaging matrix is 64 to 512 × 48 to 512.
(3) In the above (1) or (2), the repetition time TR is set to 2.0 ms to 20.0 ms, the echo time TE is set to 1.0 ms to 10.0 ms, and the flip angle FA is set to 30 ° to 90 °. A method of operating the described MRI apparatus.

According to the method of the present invention, a cerebral blood flow test can be performed with a high temporal resolution, and the imaging time per time is short, and a sufficient signal change can be obtained. Moreover, even if the O-17 water intravascular concentration is lowered by intravenous administration, the signal change can be sufficiently captured. Furthermore, special hardware is required for MRI imaging using a resonance frequency of ¹⁷ O, but in the present invention, imaging at a resonance frequency of protons is possible using a MRI apparatus that is generally used.

It is a graph which shows the relationship between the signal value obtained by MRI measurement, and O-17 water concentration value. It is a graph which shows the time density | concentration curve of O-17 water in one position of an imaging matrix. It is a map of the maximum density (reflecting cerebral blood volume CBV) in a time density curve. It is a map of the area under a curve (reflecting cerebral blood volume CBV) in a time concentration curve. It is a map of the maximum inclination (reflecting cerebral blood flow volume CBF) in a time concentration curve.

Hereinafter, the present invention will be described in detail.
The operation method of the MRI apparatus according to the present invention uses the Balanced SSFP method as an imaging sequence, and repeats a step of obtaining a signal value derived from O-17 water in the subject's cerebral blood flow and a step of obtaining the signal value a plurality of times. Obtaining a time variation curve of the signal value, obtaining a time concentration curve of O-17 water from the time variation of the signal value based on the relationship between the signal value obtained in advance and the O-17 water concentration value; Obtaining a cerebral blood flow (CBF) and / or a cerebral blood volume (CBV) from a time concentration curve.

O-17 water is water containing a higher concentration of H ₂ ¹⁷ O than in the natural state. The concentration of H ₂ ¹⁷ O is not particularly limited, but is preferably a high concentration, for example, 10% by weight or more. Such O-17 water can be produced by a method as appropriate. For example, after ¹⁷ O is concentrated by low-temperature distillation of raw material oxygen containing ¹⁷ O in advance, hydrogen is added to the concentrate. These can be obtained by reacting them (see JP 2000-218134 A).

The O-17 water to be administered to the subject may contain other components as long as the effects of the present invention are not impaired. Specifically, isotonic agents such as glucose, sodium chloride, potassium chloride, D-sorbitol, D-mannitol, glycerin, benzyl alcohol, phenethyl alcohol, sorbic acid, parahydroxybenzoic acid ester, dehydroacetic acid, chlorobutanol, etc. Preservatives, ascorbic acid, α-tocophenol, sulfite, ascorbic acid and other antioxidants, phosphates, carbonates, acetates, citrates and other buffers, mannitol and other hypertonic solutions Can do. The content of other components is preferably less than 10% by weight in total in O-17 water. As a specific example of the composition of O-17 water, for example, it contains 10 to 50% by weight of H ₂ ¹⁷ O, and further 0.1 to 0.2 mol / l sodium ion is added, and the pH is 4.5 to 8. O-17 water prepared to 0 is mentioned.

Since O-17 water is a stable isotope, there is no exposure, and since it is water, there is no allergic reaction. This O-17 water can be administered to a subject by various methods, but it is preferably administered intravenously in order to increase the blood concentration conveniently and quickly. For intravenous administration, the intravascular concentration of ¹⁷ O is usually low, but sufficient signal changes can be detected according to the present invention. Specifically, for example, it can inject | pour from an elbow vein with an injector. The O-17 water intravenously injected by the injector flows into the cerebral artery via the heart and lungs. Then, it flows out from the cerebral artery to the cerebral vein through the capillaries in the brain tissue. The dosage of O-17 water can be set as appropriate. For example, 10 to 100 ml of O-17 water per adult can be rapidly and rapidly administered at a rate of 3 ml / second or more.

  In the present invention, the Balanced SSFP method is used as the imaging sequence of the MRI apparatus. The Balanced SSFP method is one of fast gradient echo methods using a steady state. In this imaging sequence, RF pulses are applied at short intervals, so that sufficient recovery of longitudinal magnetization cannot be obtained, and two phenomena occur. One is a steady state by balancing the amount of decrease and recovery of longitudinal magnetization within each repetition time TR, and the other is an echo (spin echo and stimulated echo) due to residual transverse magnetization and RF pulses. Formation. These signals overlap in a complex manner when the RF pulses continue at regular intervals. Normally, this echo signal and FID (free induction decay) are not collected at the same time, but in the Balanced SSFP method, correction is applied to the gradient magnetic field for slice selection and the read gradient magnetic field, and overlapping signals are collected simultaneously. become. Therefore, the obtained signal is much stronger than the conventional high-speed gradient echo method, and greatly reflects the T2 value of the target blood. The Balanced SSFP method includes 2D imaging and 3D imaging, but 3D imaging is desirable in order to cover a sufficient imaging range with a thin slice thickness.

  The signal intensity according to the Balanced SSFP method depends on the ratio of T1 and T2 of the tissue. Therefore, cerebrospinal fluid in which T2 / T1 takes a relatively large value exhibits a high signal and apparently shows a contrast similar to a T2-weighted image. The signal strength is also affected by the flip angle FA, which can be a major factor in determining the image quality, but it is possible to calculate the flip angle FA necessary to obtain high contrast by simulation using the T1 and T2 values of blood. it can. A preferred flip angle FA is 30 ° to 90 °.

  The Balanced SSFP method requires several minutes for one imaging if the conventional conditions are applied as they are, and may not be sufficient as the time resolution required for cerebral blood flow measurement. In that case, the conditions can be optimized for cerebral blood flow measurement. Specifically, the imaging matrix is reduced in order to reduce the spatial resolution and increase the temporal resolution. For example, it is preferable to reduce the size to 64 to 512 × 48 to 512. Particularly preferably, it is 64 to 128 × 64 to 128. Further, by reducing the repetition time TR and the echo time TE to the limit, for example, a high time resolution of 3 seconds per time phase can be realized. The optimum ranges of TR and TE are not particularly limited, but it is preferable that TR is 2.0 ms to 20.0 ms and TE is 1.0 ms to 10.0 ms. Particularly preferably, TR is 2.0 ms to 3.0 ms and TE is 1.0 ms to 2.0 ms.

  When TR and TE are set within the above range, the phase shift of the off-resonance spin that occurs within the repetition time TR continues to accumulate in this sequence that does not use the spoiling technique, and the signal is canceled due to the phase difference. By matching, a black band called a banding artifact is generated on the image. This banding artifact can be moved from within the imaging range by modulating the phase of a radio wave (RF wave). For example, by modulating the phase of the RF wave from 0 ° to 360 °, it is possible to move from the region of interest within the imaging range to an arbitrary location.

  As described above, for example, by continuously repeating the imaging at a high speed of 3 seconds per time phase a plurality of times, the time change of the signal value derived from the O-17 water in the cerebral blood flow can be obtained. Here, based on the correlation between the signal value obtained in advance and the O-17 water concentration value, the signal value is converted into the O-17 water concentration, and the time concentration curve of the O-17 water from the time change of the signal value. Can be obtained. From this time density curve, the cerebral blood flow (CBF, mL / 100 g / min) and the cerebral blood volume (CBV, mL / 100 g) at each position (one pixel) of the imaging matrix can be obtained. Specifically, the maximum slope of the time concentration curve corresponds to cerebral blood flow (CBF), and the maximum concentration and the area under the curve correspond to cerebral blood volume (CBV). The calculation of the CBF value based on the maximum gradient method is obtained by dividing the maximum value of the gradient in the time density curve of each pixel by the maximum density of the artery. The CBV value is obtained by dividing the maximum density in the time density curve of each pixel by the maximum density of the artery or vein, or by dividing the area under the curve in the time density curve of each pixel by the area under the curve of the artery or vein. It is done.

  Then, by integrating information on the maximum slope, maximum density and area under the curve obtained from the time density curve in each pixel of the imaging matrix, a map of the maximum slope, maximum density and area under the curve of the entire brain, that is, cerebral blood flow A map of (CBF) and cerebral blood volume (CBV) can be created. In the present invention, both CBF and CBV maps may be created, or one of them may be created. The values of cerebral blood flow and cerebral blood volume are converted into color information by conversion using a color look-up table and imaged. Since high-density pixels of cerebrospinal fluid are conspicuous when imaging, a map that is easy to visually recognize is created by masking pixels with a certain density or higher.

Next, the present invention will be described in more detail based on examples, but the present invention is not limited thereto.
Example 1
First, nine types of O-17 water having different concentrations (0.037 wt% to 1.566 wt%) were prepared, and imaging of these O-17 water phantoms was performed. Imaging conditions are as follows. FIG. 1 shows the relationship between the O-17 water concentration and the signal intensity (logarithmic ratio) obtained as a result of the measurement. By using this regression line, the signal value can be converted into O-17 water concentration.
(Phantom imaging conditions)
3.0T (GEHC, Sigma Excite HD)
QD head coil
FOV: 180x120mm
Imaging matrix: 160 × 160
Slice thickness: 3mm
Number of slices: 40 slices Flip angle: 50 °
TR: 2.97ms
TE: 1.04ms

Next, imaging was performed on eight beagle dogs (female).
Age: 10.6 ± 3.9 months (6-19 months)
Body weight: 10.5 ± 1.3 kg (9.1 to 11.9 kg)
Premedication:
Medetomidine (10 μg / kg)
Midazolam (0.3mg / kg)
Butorphanol (0.2mg / kg)
Intravenous anesthesia:
1% propofol (4-6 mg / kg bolus administration + 1.2 mg / kg / h infusion)

Based on the Balanced SSFP method, the imaging was performed by reducing the imaging matrix to 64 × 60 and reducing TR and TE to the minimum in order to reduce the spatial resolution and increase the temporal resolution. Simultaneous imaging of 12 slices was performed by the 3D method, imaging for 3 seconds per hour phase was repeated 120 times, and imaging was performed for a total of 6 minutes. The imaging conditions are summarized below.
(Beagle dog imaging conditions)
MRI
3.0T (GEHC, Sigma Excite HD)
QD head coil
FOV: 240x120mm
Imaging matrix: 64 × 60
Slice thickness: 8mm
Number of slices: 12 slices FA: 60 °
TR: 2.6 ms
TE: 1.22ms
BW: 20.83
Scan duration: 3 seconds x 120 times (6 minutes)

  About 25 seconds after the start of imaging, about 75 seconds, 10 wt% O-17 water was intravenously injected. O-17 water was distilled and purified, and 0.9 w / v% sodium chloride was used as physiological saline. The dose is 1.0 ml / kg. The time concentration curve of O-17 water obtained for one pixel is shown in FIG. In FIG. 2, the curve of (a) represents the time concentration curve of O-17 water. The curve (b) is a signal curve of the entire image and can be ignored here. The straight line (c) represents the natural concentration of O-17 water and is a signal stable point. It can be seen that the signal is not stable for about 30 seconds after the start of imaging. In addition, although it seems that O-17 water exists before injection | pouring of O-17 water, it is the range of an error.

  From the obtained time concentration curve, the maximum concentration, the maximum slope and the area under the curve were calculated. The maximum slope corresponds to the semi-quantitative value of cerebral blood flow (CBF), and the maximum concentration and the area under the curve correspond to the semi-quantitative value of cerebral blood volume (CBV). A map was created by integrating the maximum density, maximum slope and area under the curve obtained for each position of the imaging matrix. 3 to 5 are excerpts of 8 out of 12 slices, respectively, and FIG. 3 is a map of maximum concentration, which reflects cerebral blood volume (CBV). FIG. 4 is a map of the area under the curve and reflects the cerebral blood volume (CBV). Further, FIG. 5 is a map of maximum slope, which reflects cerebral blood flow (CBF). As shown in FIGS. 3 to 5, information on cerebral blood flow (CBF) and cerebral blood volume (CBV) of beagle dogs could be obtained with high temporal resolution.

  According to the present invention, a cerebral blood flow test can be easily performed in many facilities, and can play a major role in the prevention and treatment strategies of stroke, which has become a major social problem in Japan. In addition, the high-resolution cerebral blood flow image obtained by the present invention makes it possible to capture changes in blood flow in small areas of the cerebral cortex and small nerve nuclei in the brain stem, etc. It may lead to the elucidation and early detection of disease states such as dementia such as Alzheimer's disease, mental disorders such as depression and schizophrenia.

  Furthermore, at present, high-concentration O-17 water is expensive, but if the clinical significance of the present invention as a cerebral blood flow test is demonstrated, domestic industry promotion such as improvement of purification technology and development of mass production plants will be performed. It is expected to lead to.

Claims (3)

Using the Balanced SSFP method as an imaging sequence, obtaining a signal value derived from O-17 water in the subject's cerebral blood flow;
Repeating the step of obtaining the signal value a plurality of times to obtain a time change of the signal value;
Obtaining a time concentration curve of O-17 water from the time change of the signal value based on the relationship between the signal value obtained in advance and the O-17 water concentration value;
Determining cerebral blood flow (CBF) and / or cerebral blood volume (CBV) from the time concentration curve;
Integrating the cerebral blood flow (CBF) and / or cerebral blood volume (CBV) obtained for each position of the imaging matrix to create a map of cerebral blood flow (CBF) and / or cerebral blood volume (CBV) And a method of operating the MRI apparatus in imaging cerebral blood flow.   The operation method of the MRI apparatus according to claim 1, wherein the imaging matrix is 64 to 512 × 48 to 512. The operation of the MRI apparatus according to claim 1 or 2, wherein the repetition time TR is set to 2.0 ms to 20.0 ms, the echo time TE is set to 1.0 ms to 10.0 ms, and the flip angle FA is set to 30 ° to 90 °. Method.

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