Magnetic resonance imaging apparatus, chemical shift peak detection method, and contrast agent nanoparticle

Abstract

To shorten an imaging time and improve detection accuracy for a peak of a chemical shift.SOLUTION: A MRI apparatus according to the present embodiment includes: a stimulation application unit that applies a dissolution stimulus to contrast agent nanoparticles accumulated in an imaging region after the contrast agent nanoparticles are injected into a subject; a collection unit that collects a first magnetic resonance signal group through CEST imaging while varying saturation pulse conditions before contrast imaging by the contrast agent nanoparticles, and collects a second magnetic resonance signal group through the CEST imaging while varying the saturation pulse conditions after contrast imaging by the contrast agent nanoparticles and after application of the dissolution stimulus by the stimulation application unit; a calculation unit that calculates a difference between a first Z-spectrum generated on the basis of the first magnetic resonance signal group and a second Z-spectrum generated on the basis of the second magnetic resonance signal group; and a detection unit that detects multiple peaks indicating decreases in magnetic resonance signals due to chemical shifts on the basis of the difference.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The embodiments disclosed in this specification and the drawings relate to a magnetic resonance imaging apparatus, a chemical shift peak detection method, and contrast agent nanoparticles.

Background Art

[0002] Protons present in a solute in water have a specific resonance frequency for each solute and are chemically exchanged (Chemical Exchange) with the protons of water. Therefore, when a saturation pulse is selectively transmitted to the protons of the solute, the saturated protons are exchanged with the unsaturated protons of water by the chemical exchange phenomenon, and the saturated protons move to the water (Saturation Transfer). This phenomenon is generally called Chemical Exchange Saturation Transfer (CEST), and the rate K of chemical exchange in CEST ex depends on temperature and pH and can be used for their measurement. Imaging techniques using the CEST phenomenon (for example, an MR imaging technique utilizing the exchange between protons such as an amide group (-C(=O)-NH-), a hydroxy group (-OH), and an amino group (-NH 2 2)) and the protons in free water) are called CEST imaging (CRST imaging). At this time, a substance that realizes the CEST phenomenon (hereinafter referred to as a CEST substance) is used in CEST imaging. FIG. 3 is a diagram for explaining the outline of CEST. From A to B in FIG. 3 shows the step of selectively saturating the protons of the CEST substance, and from B to C in FIG. 3 shows the step of exchanging the saturated protons of the CEST substance with the protons of free water.

[0003] The CEST phenomenon reflects the properties of substances such as temperature and pH. That is, the rate of chemical exchange in the CEST phenomenon depends on temperature and pH. Therefore, CEST imaging can be used for the measurement of temperature and pH. For example, by combining a CEST substance having two proton pools with a technique called the ratiometric method, pH imaging capable of imaging pH regardless of the concentration of the CEST substance has been made possible. In the calculation of pH by the ratiometric method, in the Z spectrum showing the influence of the CEST effect, for example, the signal values at two peaks related to the two proton pools and the signal value used for the normalization of the signal values in the Z spectrum are used. To obtain the data used for generating the Z spectrum, a magnetic resonance imaging technique related to the CEST effect (hereinafter referred to as CEST imaging) is executed. Figure 4 is a diagram showing an example of an overview from conventional CEST imaging to the generation of a Z spectrum and the detection of peaks in a CEST substance. The CEST substance shown in Figure 4 is ioversol, which corresponds to two substances, two amide groups corresponding to a chemical shift of 4.2 ppm and one amide group corresponding to a chemical shift of 5.6 ppm. In Figure 4, it is assumed that the frequencies of a plurality of saturation pulses used for CEST imaging are at intervals of 0.1 ppm in the range from -10 ppm to 10 ppm. For example, when the static magnetic field strength is 3 T, the frequency of the saturation pulse corresponding to 0 ppm is the resonance frequency of free water based on the static magnetic field strength (hereinafter referred to as the center frequency), which is 128 MHz. At this time, the frequency of the saturation pulse corresponding to +10 ppm is (128 MHz + 128 × 10 Hz). On the other hand, the frequency of the saturation pulse corresponding to -10 ppm is (128 MHz - 128 × 10 Hz). As shown in FIG. 4, according to CEST imaging, an MR image (CEST image) is acquired as a plurality of saturation pulses with a center frequency of 0 ppm and a step of 0.1 ppm from -10 ppm to +10 ppm are applied. Signal data is acquired based on the pixel values within the region of interest (ROI) (ROI1 and ROI2 in FIG. 4) in 201 MR images. A Z spectrum is generated based on the acquired signal data. Next, the signal value (peak) at the chemical shift (ppm) regarding the CEST substance in the Z spectrum is detected. As shown in FIG. 4, in conventional CEST imaging, there is a problem that the imaging time becomes long in order to obtain 201 CEST images. In addition, when obtaining a Z spectrum with less noise, since a plurality of Z spectra are generated, there is a problem that the imaging time becomes even longer. Also, as shown in FIG. 4, when detecting two peaks of the CEST substance in the Z spectrum, considering all the natural proton pools in the living body, fitting is required by five approximate formulas (two approximate formulas corresponding to the two peaks of the two CEST substances, an approximate formula regarding the peak of water, an approximate formula regarding the MT (Magnetization Transfer) effect, and an approximate formula regarding the overhausser effect). The fitting by these five approximate formulas is complicated and time-consuming, and the fitting accuracy may deteriorate. In addition, since the initial values of the parameters in the five approximate formulas vary depending on the tissue from which the Z spectrum is obtained, it is necessary to set the initial values according to the tissue.

[0004] The EPR (Enhanced Permeability and Retention) effect is a phenomenon in which the substance permeability of blood vessels and the retention of the permeated substances are enhanced in tumor tissues. As shown in FIG. 5, the blood vessels 1101 near the tumor 1103 have large gaps (150 nm or more), and the substances in the blood flow leak out and remain in the tumor tissue (EPR effect), while the blood vessels 1102 of the normal tissue 1104 have small gaps (about 5 to 50 nm), so that the necessary nutrients in the blood flow reach the normal tissue 1104. In addition, aiming at the EPR effect, proposals have been made to encapsulate various substances in nanoparticles, and nanoparticles 1201 encapsulating a CEST substance 1202 (for example, iopamidol) as shown in FIG. 6 have also been proposed.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Non-Patent Documents

[0006]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0007] In an imaging apparatus and an imaging method using a CEST substance as a contrast agent, a substance that causes the CEST phenomenon is required in a sufficient amount to a certain extent. In the case of a method of encapsulating a CEST substance in nanoparticles, if the nanoparticles disintegrate in the blood or the nanoparticles do not disintegrate in the target tumor and the release of the CEST substance is delayed, it takes time for the CEST substance to accumulate in the tumor, and imaging after waiting for the accumulation results in long-time imaging.

[0008] One of the problems to be solved by the embodiments disclosed in this specification and the drawings is to shorten the imaging time and improve the detection accuracy of chemical peak shifts. However, the problems to be solved by the embodiments disclosed in this specification and the drawings are not limited to the above problems. The problems corresponding to the effects of each configuration shown in the embodiments described later can also be regarded as other problems.

Means for Solving the Problems

[0009] The magnetic resonance imaging apparatus according to this embodiment includes a stimulation unit that applies a dissolution stimulation to the contrast agent nanoparticles accumulated in the imaging region after injecting the contrast agent nanoparticles into a subject, and before contrast imaging with the contrast agent nanoparticles, a first magnetic resonance signal group is collected by CEST (Chemical Exchange Saturation Transfer) imaging while changing the conditions of a saturation pulse, and after contrast imaging with the contrast agent nanoparticles and after the dissolution stimulation is applied by the stimulation unit, a second magnetic resonance signal group is collected by the CEST imaging while changing the conditions of the saturation pulse, a calculation unit that calculates the difference between a first Z spectrum generated based on the first magnetic resonance signal group and a second Z spectrum generated based on the second magnetic resonance signal group, and a detection unit that detects a plurality of peaks indicating a decrease in the magnetic resonance signal due to chemical shift based on the difference.

Brief Description of the Drawings

[0010]

Figure 1

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Embodiments for Carrying Out the Invention

[0011] Hereinafter, with reference to the drawings, embodiments of a magnetic resonance imaging apparatus (hereinafter referred to as an MRI (Magnetic Resonance Imaging) apparatus), a chemical shift peak detection method, and contrast agent nanoparticles will be described. Note that the embodiments are not limited to the following embodiments. In addition, the contents described in each embodiment can be similarly applied to other embodiments in principle. In the following embodiments, parts denoted by the same reference numerals perform the same operations, and overlapping explanations will be omitted as appropriate.

[0012] FIG. 7 is a block diagram showing the configuration of the MRI apparatus 100 according to the embodiment. As shown in FIG. 7, the MRI apparatus 100 includes a static magnetic field magnet 101, a static magnetic field power supply 102, a gradient magnetic field coil 103, a gradient magnetic field power supply 104, a bed 105, a bed control circuit 106, a transmission coil 107, a transmission circuit 108, a reception coil 109, a reception circuit 110, a sequence control circuit 120, a computer 130 (also referred to as an image processing apparatus), and a stimulation applying mechanism 160. Note that the MRI apparatus 100 does not include a subject P (for example, a human body). Also, the configuration shown in FIG. 7 is merely an example. For example, each part in the sequence control circuit 120 and the computer 130 may be appropriately integrated or separated. The computer 130 is mounted on, for example, a console. For example, the stimulation applying mechanism 160 may be arranged at a distance from the subject P as shown in the figure, or may be arranged in close contact with the subject P.

[0013] The static magnetic field magnet 101 is a magnet formed in a hollow substantially cylindrical shape, and generates a static magnetic field in the internal space. The static magnetic field magnet 101 is, for example, a superconducting magnet or the like, and is excited by receiving current supply from the static magnetic field power supply 102. The static magnetic field power supply 102 supplies current to the static magnetic field magnet 101. Note that the static magnetic field magnet 101 may be a permanent magnet, and in this case, the MRI apparatus 100 may not include the static magnetic field power supply 102. Also, the static magnetic field power supply 102 may be provided separately from the MRI apparatus 100.

[0014] The gradient magnetic field coil 103 is a coil formed in a hollow substantially cylindrical shape, and is arranged inside the static magnetic field magnet 101. The gradient magnetic field coil 103 is formed by combining three coils corresponding to the X, Y, and Z axes orthogonal to each other, and these three coils receive current supply individually from the gradient magnetic field power supply 104 to generate a gradient magnetic field in which the magnetic field strength changes along the X, Y, and Z axes. The gradient magnetic fields along the X, Y, and Z axes generated by the gradient magnetic field coil 103 are, for example, a slice gradient magnetic field Gs, a phase encoding gradient magnetic field Ge, and a readout gradient magnetic field Gr. The gradient magnetic field power supply 104 supplies current to the gradient magnetic field coil 103.

[0015] The examination table 105 includes a top plate 105a on which the subject P is placed. Under the control of the examination table control circuit 106, the top plate 105a is inserted into the cavity (imaging opening) of the gradient magnetic field coil 103 with the subject P placed thereon. Usually, the examination table 105 is installed such that its longitudinal direction is parallel to the central axis of the static magnetic field magnet 101. The examination table control circuit 106 drives the examination table 105 under the control of the computer 130 to move the top plate 105a in the longitudinal direction and the vertical direction.

[0016] The transmission coil 107 is disposed inside the gradient magnetic field coil 103, receives the supply of RF pulses from the transmission circuit 108, and generates a high-frequency magnetic field. The transmission circuit 108 supplies an RF pulse corresponding to the Larmor frequency determined by the type of the target atom and the magnetic field strength to the transmission coil 107.

[0017] The reception coil 109 is disposed inside the gradient magnetic field coil 103 and receives a magnetic resonance signal (hereinafter referred to as an MR (Magnetic Resonance) signal) emitted from the subject P due to the influence of the high-frequency magnetic field. When the reception coil 109 receives the MR signal, the reception coil 109 outputs the received MR signal to the reception circuit 110.

[0018] Note that the above-described transmission coil 107 and reception coil 109 are merely examples. The transmission coil 107 and the reception coil 109 may be configured by combining one or a plurality of coils having only a transmission function, coils having only a reception function, or coils having a transmission and reception function.

[0019] The reception circuit 110 detects the MR signal output from the reception coil 109 and generates MR data based on the detected MR signal. Specifically, the reception circuit 110 generates MR data by digitally converting the MR signal output from the reception coil 109. Further, the reception circuit 110 transmits the generated MR data to the sequence control circuit 120. Note that the reception circuit 110 may be provided on the gantry device side including the static magnetic field magnet 101, the gradient magnetic field coil 103, and the like.

[0020] The sequence control circuit 120 has a collection function 121. The collection function 121 performs imaging of the subject P by driving the gradient magnetic field power supply 104, the transmission circuit 108, and the reception circuit 110 based on the sequence information transmitted from the computer 130. Here, the sequence information is information that defines the procedure for performing imaging, and is also referred to as sequence conditions. The sequence information defines the strength of the current supplied by the gradient magnetic field power supply 104 to the gradient magnetic field coil 103, the timing of supplying the current, the intensity of the RF pulse supplied by the transmission circuit 108 to the transmission coil 107, the timing of applying the RF pulse, the timing at which the reception circuit 110 detects the MR signal, and the like.

[0021] The sequence control circuit 120 is, for example, an integrated circuit such as an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), an electronic circuit such as a central processing unit (CPU), or a micro processing unit (MPU). The sequence control circuit 120 corresponds to a sequence control unit. Further, the sequence control circuit 120 that realizes the collection function 121 corresponds to a collection unit.

[0022] The acquisition function 121 collects a first magnetic resonance signal group while changing the conditions of the saturation pulse with respect to the frequency band determined by the determination function 138 described later, by performing CEST imaging (hereinafter referred to as non-contrast CEST imaging) of the subject P before contrast with a contrast agent (contrast substance). Further, the acquisition function 121 collects a second magnetic resonance signal group while changing the conditions of the saturation pulse with respect to the frequency band determined by the determination function 138, by performing CEST imaging (hereinafter referred to as contrast CEST imaging) of the subject P after contrast with the contrast agent. As sequences for non-contrast CEST imaging and contrast CEST imaging, known sequences can be used except that the frequency of the saturation pulse is within the determined frequency band, so the description thereof is omitted. Also, CEST imaging and the frequency band will be described later. When the acquisition function 121 drives the gradient magnetic field power supply 104, the transmission circuit 108, and the reception circuit 110 to image the subject P and receives MR data from the reception circuit 110, the acquired MR data is transferred to the computer 130.

[0023] The computer 130 performs overall control of the MRI apparatus 100, generation of images, etc. The computer 130 includes a storage circuit 132, an input device 141, a display 143, and a processing circuit 150. The processing circuit 150 includes an interface function 131, a control function 133, an image generation function 134, an acquisition function 136, a determination function 138, a calculation function 140, and a detection function 142.

[0024] Each processing function performed by the interface function 131, the control function 133, the image generation function 134, the acquisition function 136, the determination function 138, the calculation function 140, and the detection function 142 is stored in the storage circuit 132 in the form of a program executable by the computer 130. The processing circuit 150 is a processor that reads a program from the storage circuit 132 and executes it to realize the functions corresponding to the respective programs. In other words, the processing circuit 150 in the state of having read each program has each function shown in the processing circuit 150 of FIG. 7.

[0025] In FIG. 7, the processing functions performed by the interface function 131, the control function 133, the image generation function 134, the acquisition function 136, the determination function 138, the calculation function 140, and the detection function 142 are described as being realized by a single processing circuit 150. However, it is also possible to configure the processing circuit 150 by combining a plurality of independent processors, and each processor realizes a function by executing a program. In other words, each of the above functions may be configured as a program, and it may be the case where a single processing circuit 150 executes each program, or it may be the case where a specific function is implemented in a dedicated independent program execution circuit.

[0026] The term "processor" used in the above description means a circuit such as, for example, a CPU, a GPU (Graphical Processing Unit), or an application-specific integrated circuit, a programmable logic device (for example, a simple programmable logic device (SPLD), a complex programmable logic device (CPLD), and a field programmable gate array FPGA). The processor realizes a function by reading and executing a program stored in the storage circuit 132.

[0027] Note that instead of storing a program in the storage circuit 132, it may be configured to directly incorporate the program into the circuit of the processor. In this case, the processor realizes a function by reading and executing the program incorporated in the circuit. Note that the bed control circuit 106, the transmission circuit 108, the reception circuit 110, the sequence control circuit 120, etc. are also similarly constituted by the above electronic circuits such as the processor.

[0028] The memory circuit 132 stores MR data received by the processing circuit 150 having the interface function 131, various data acquired by the acquisition function 136, various image data generated by the image generation function 134, the calculation processing used in the calculation function 140, the difference calculated by the calculation processing, and the detection processing used in the detection function 142. The memory circuit 132 also stores a plurality of peaks determined by the detection function 144 and the like.

[0029] In addition, the memory circuit 132 stores MR data (also referred to as k-space data) arranged in the k-space by the control function 133. These various stored data will be described later. For example, the memory circuit 132 is realized by a semiconductor memory element such as a RAM (Random Access Memory), a flash memory, a hard disk, an optical disk, or the like. The memory circuit 132 may be referred to as a memory.

[0030] The input device 141 receives various instructions and information inputs from the user. The input device 141 is realized by, for example, a trackball, a switch button, a mouse, a keyboard, a touch pad that performs an input operation by touching an operation surface, a touch screen in which a display screen and a touch pad are integrated, a non-contact input circuit using an optical sensor, and a voice input circuit. The input device 141 is electrically connected to the processing circuit 150, and converts the input operation received from the user into an electrical signal and outputs it to the processing circuit 150.

[0031] Note that in this specification, the input device 141 is not limited to only those having physical operation components (input interfaces) such as a mouse and a keyboard. For example, an electrical signal processing circuit that receives an electrical signal corresponding to an input operation from an external input device provided separately from the MRI apparatus 100 and outputs this electrical signal to the control circuit is also included in the example of the input device 141. The input device 141 corresponds to an input unit and may be referred to as an input interface.

[0032] The display 143 receives inputs such as imaging conditions through a GUI (Graphical User Interface) under the control of a processing circuit 150 having a control function 133, and displays images generated by the processing circuit 150 having an image generation function 134, etc. The display 143 is realized by, for example, a display device such as a CRT display, a liquid crystal display, an organic EL display, an LED display, a plasma display, or any other display or monitor known in the art.

[0033] Hereinafter, an example of CEST imaging according to this embodiment will be described. In CEST imaging, the sequence control circuit 120 applies a saturation pulse, which is a frequency-selective RF (Radio Frequency) pulse, at a frequency away from the resonance frequency of free water (off-resonance frequency) and at the resonance frequency of exchangeable protons (e.g., protons of a compound), to the subject P before collecting the MR signal. The saturation pulse is also referred to as a presaturation pulse. CEST imaging is a magnetic resonance imaging technique that performs the application of a plurality of saturation pulses and the collection of a plurality of magnetic resonance signals (MR signals) corresponding to the plurality of saturation pulses. The frequency of each of the plurality of saturation pulses used in CEST imaging is determined by a determination function 138 described later. Note that, regarding the frequencies of the plurality of saturation pulses, the interval between the frequencies of two adjacent saturation pulses is described as 0.1 ppm. Note that the interval between the frequencies of two adjacent saturation pulses is not limited to 0.1 ppm and can be arbitrarily set as long as a Z spectrum that clarifies the CEST phenomenon can be drawn.

[0034] Hereinafter, for the sake of specificity in the description, a plurality of substances (a plurality of CEST substances: proton pools) that realize the CEST phenomenon are assumed to be included in the contrast agent. That is, the contrast agent contains a plurality of substances (functional groups) with different chemical shifts from each other. For example, when the contrast agent is iopamidol, iopamidol contains two substances (two types of amide groups) with different chemical shifts from each other. Specifically, the two substances contained in iopamidol correspond to two types of substances, namely, two amide groups corresponding to a chemical shift of 4.2 ppm and one amide group corresponding to a chemical shift of 5.6 ppm. Note that the contrast agent in the present embodiment is not limited to iopamidol, and any contrast agent can be applied as long as it has a plurality of CEST substances with different chemical shifts from each other.

[0035] The contrast agent according to the embodiment is used in the form of contrast agent nanoparticles obtained by encapsulating the contrast agent in stimulus-responsive nanoparticles. As the stimulus-responsive nanoparticles, liposomes are preferable. It is preferable that the liposomes are surface-modified. As the surface modification, for example, polyethylene glycol (PEG) modification is preferable in terms of improving the stability of liposomes in blood, and modification with a metal, a metal complex, or a metal ion is preferable in terms of making it easier to monitor the accumulation of contrast agent nanoparticles at the imaging target site. Modification with a metal ion that greatly changes the relaxation time of the contrast agent nanoparticles is more preferable. The diameter of the contrast agent nanoparticles is not particularly limited, but is preferably 10 to 100 nm, and more preferably 50 to 100 nm. When the diameter of the contrast agent nanoparticles is 10 nm or more, it is not easy to pass through the gaps in the blood vessels of normal tissues and it is difficult to leak from the blood vessels. On the other hand, in the blood vessels near the tumor, it is easy to pass through the gaps and it is easy to leak out of the blood vessels and accumulate in the tumor (EPR effect). Note that the diameter of the contrast agent nanoparticles is the arithmetic mean particle diameter calculated by performing particle size distribution measurement by the laser method.

[0036] The processing circuit 150 transmits sequence information to the sequence control circuit 120 and receives MR data from the sequence control circuit 120 through the interface function 131. Also, when receiving MR data, the processing circuit 150 having the interface function 131 stores the received MR data in the storage circuit 132. The processing circuit 150 that realizes the interface function 131 corresponds to the interface unit.

[0037] The processing circuit 150 performs overall control of the MRI apparatus 100 and controls imaging, image generation, image display, etc. through the control function 133. For example, the processing circuit 150 having the control function 133 receives input of imaging conditions (imaging parameters, etc.) on the GUI and generates sequence information according to the conditions of the saturation pulse set by the received imaging conditions. Also, the processing circuit 150 having the control function 133 transmits the generated sequence information to the sequence control circuit 120.

[0038] For example, the control function 133 transmits, to the sequence control circuit 120, sequence information of CEST imaging including a plurality of frequencies related to the saturation pulse in the frequency band determined by the determination function 13, and sequence information of MR imaging (hereinafter referred to as map imaging) for collecting MR data related to the generation of the B 0 map. The processing circuit 150 that realizes the control function 133 corresponds to the control unit.

[0039] The processing circuit 150 reads k-space data from the storage circuit 132 and generates an image by performing reconstruction processing such as Fourier transform on the read k-space data through the image generation function 134. For example, the image generation function 134 generates a B 0 map based on the MR data (hereinafter referred to as map MR data) collected by map imaging. The B 0 map is a map showing the inhomogeneity of the static magnetic field (B 0 ) in the imaging region. The image generation function 134 stores the generated B 0 map in the storage circuit 132. The B 0Since the generation of the map can appropriately utilize known methods, the description thereof is omitted. The processing circuit 150 that realizes the image generation function 134 corresponds to an image generation unit.

[0040] The processing circuit 150 generates a first Z spectrum based on the first magnetic resonance signal group by the image generation function 134. Specifically, the image generation function 134 generates a plurality of MR images (hereinafter referred to as non-contrast MR images) based on the first magnetic resonance signal group (non-contrast data) collected by CEST imaging before contrast agent injection (non-contrast). The image generation function 134 corrects the position of the saturation pulse (hereinafter referred to as B 0 correction) based on the plurality of non-contrast MR images and the B 0 map, and generates a first Z spectrum (non-contrast Z spectrum). Note that the B 0 correction may be performed on the contrast-enhanced MR images. At this time, the image generation function 134 generates a first Z spectrum based on the plurality of contrast-enhanced MR images on which the B 0 correction has been performed. At this time, the first Z spectrum is normalized by a reference MR signal described later. That is, the first Z spectrum is generated based on the first magnetic resonance signal group and the reference MR signal. Since known methods are applicable to the generation of the Z spectrum, the description thereof is omitted. Note that the B 0 correction may be omitted.

[0041] The processing circuit 150 generates a second Z spectrum based on the second magnetic resonance signal group by the image generation function 134. Specifically, the image generation function 134 generates a plurality of MR images (hereinafter referred to as contrast-enhanced MR images) based on the second magnetic resonance signal group (contrast data) collected by CEST imaging after contrast agent injection. The image generation function 134 generates a second Z spectrum (contrast Z spectrum) with B 0 correction based on the plurality of contrast-enhanced MR images and the B 0 map. Note that the B 0 correction may be performed on the contrast-enhanced MR images. At this time, the image generation function 134 0A second Z spectrum is generated based on a plurality of contrast-enhanced MR images on which corrections have been performed. At this time, the second Z spectrum is normalized by a reference MR signal described later. That is, the second Z spectrum is generated based on a second group of magnetic resonance signals and the reference MR signal.

[0042] The first Z spectrum and the second Z spectrum are B generated by an imaging different from CEST imaging 0 Based on the map, the position of the saturation pulse in CEST imaging is corrected, and it is a Z spectrum normalized by the reference MR signal. The processing circuit 150 that realizes the image generation function 134 corresponds to an image generation unit. Note that the generation of the first Z spectrum and the second Z spectrum may be generated by the computing function 140.

[0043] The processing circuit 150 acquires information on a contrast agent containing a plurality of substances having different chemical shifts through the acquisition function 136. Specifically, the acquisition function 136 acquires information on the contrast agent input by the user via the input device 141. Information on the contrast agent is, for example, a plurality of chemical shifts (ppm) corresponding to a plurality of CEST substances (substances that realize the CEST phenomenon). When the name of the contrast agent is input by the user via the input device 141, the acquisition function 136 acquires information on the contrast agent by collating the correspondence table stored in the storage circuit 132 with the input name of the contrast agent. The correspondence table corresponds to, for example, a lookup table associating the name of the contrast agent with a plurality of chemical shifts (ppm). The processing circuit 150 that realizes the acquisition function 136 corresponds to an acquisition unit.

[0044] The processing circuit 150 determines, by the determination function 138, a frequency band related to the decrease in the MR signal due to the chemical shift based on the information acquired by the acquisition function 146. The frequency band corresponds to the region of the frequency of the saturation pulse related to the decrease in the MR signal due to the CEST phenomenon of each of the plurality of CEST substances, centered on each of the plurality of chemical shifts. The frequency band (which may also be referred to as a frequency region) is a predetermined range determined in the order of ppm with the saturation frequency of water being 0 ppm, and has a predetermined width centered on a unique value (chemical shift) determined by the components of the contrast agent. For example, when the plurality of chemical shifts are 4.2 ppm and 5.6 ppm, the determination function 138 determines a band including a predetermined frequency range centered on 4.2 ppm and 5.6 ppm as the above-mentioned frequency band. The predetermined frequency range is, for example, ±1 ppm. Note that the predetermined range is not limited to ±1 ppm and can be arbitrarily set as long as it is the frequency range related to the decrease in the MR signal due to the CEST phenomenon of each of the plurality of CEST substances.

[0045] Note that instead of the predetermined frequency range, the determination function 138 may use the number n of times of applying a saturation pulse along the +ppm or -ppm direction centered on each of the plurality of chemical shifts. For example, when n = 10, since the interval between the frequencies of two adjacent saturation pulses is 0.1 ppm, the frequency range is the same as above.

[0046] Also, the determination function 138 may further use the B 0 map generated before the execution of the CEST imaging to determine the above-mentioned frequency band. Specifically, the determination function 138 determines the average value of the plurality of B 0 values corresponding to the plurality of pixels included in the ROI related to the generation of the Z spectrum, or the median value of the plurality of B 0 values as the resonance frequency of water (0 ppm). Next, the determination function 138 determines the above-mentioned frequency band using the determined resonance frequency of water.

[0047] Further, the determination function 138 may determine a frequency (hereinafter referred to as a reference frequency) that is outside the determined frequency band and is not involved (irrelevant, weakly related) in the decrease of the magnetic resonance signal due to the chemical shift, based on the information acquired by the acquisition function 146. The MR signal (hereinafter referred to as a reference MR signal) collected by applying the reference frequency as a saturation pulse is used for the normalization of the signal value of the contrast-enhanced Z spectrum and the signal value of the non-contrast-enhanced Z spectrum.

[0048] Specifically, the determination function 138 determines, as the reference frequency, a frequency that is not affected by disturbances such as the saturation frequency of water, a plurality of chemical shifts related to a plurality of CEST substances, the MT effect, and the Overhauser effect. For example, the determination function 138 determines, as the reference frequency, a frequency corresponding to a ppm with an absolute value greater than ±10 ppm (that is, a ppm farther from ±10 ppm), and a frequency corresponding to -20 ppm. Note that the determination function 138 may determine, as the reference frequency, a frequency corresponding to a position where n is greater than 10. In the collection of the reference MR signal, when the saturation pulse is not applied, the determination of the reference frequency by the determination function 138 becomes unnecessary.

[0049] When the reference frequency is determined by the determination function 138, before the contrast agent is administered to the subject P, the sequence control circuit 120 uses the determined reference frequency as a saturation pulse by the collection function 121 to collect a reference MR signal that serves as a reference for the first Z spectrum and the second Z spectrum. When the reference frequency is not determined by the determination function 138, before the contrast agent is administered to the subject P, the sequence control circuit 120 collects a reference MR signal without using a saturation pulse by the collection function 121. Note that the collection of the reference MR signal may be performed by contrast-enhanced CEST imaging or by imaging separate from contrast-enhanced CEST imaging. The processing circuit 150 that realizes the determination function 138 corresponds to a determination unit.

[0050] The processing circuit 150 calculates the difference between a first Z-spectrum generated based on a first magnetic resonance signal group and a second Z-spectrum generated based on a second magnetic resonance signal group by means of the computing function 140. For example, the computing function 140 calculates the difference (hereinafter referred to as the difference spectrum) by subtracting the second Z-spectrum from the first Z-spectrum. The computing function 140 calculates a state quantity in an imaging region (e.g., ROI) regarding the first Z-spectrum and the second Z-spectrum based on a plurality of peaks detected by the detection function 142 and a reference MR signal. The state quantity is, for example, the temperature or pH in the imaging region. The calculation of pH, etc. follows, for example, the calculation procedures (e.g., Ratiometric method, etc.) described in non-patent documents, and thus the description is omitted. The computing function 140 stores the calculated state quantity in the storage circuit 132. Note that the calculated state quantity may be displayed on the display 143 by means of, for example, the control function 133. The processing circuit 150 that realizes the computing function 140 corresponds to a calculation unit.

[0051] The processing circuit 150, by means of the detection function 142, detects, for a plurality of substances, a plurality of peaks indicating a decrease in the magnetic resonance signal due to chemical shift based on the calculated difference. In other words, the detection function 142 detects, based on the difference, a plurality of peaks corresponding to the chemical shift of each of the plurality of CEST substances and indicating a decrease in the magnetic resonance signal. Specifically, the detection function 142 detects the plurality of peaks by function fitting of the signal value distribution in the calculated difference or estimation of the profile of the distribution. More specifically, the detection function 412 detects the peaks of two CEST substances by function fitting of the signal value distribution using two approximate expressions corresponding to the peaks of the two CEST substances. Note that the detection function 142 may detect the plurality of peaks by estimation of the profile (estimation of the value at the peak apex) of the signal value distribution instead of function fitting. Since known methods can be appropriately used for function fitting and profile estimation, the description is omitted. The processing circuit 150 that realizes the detection function 142 corresponds to a detection unit.

[0052] The overall configuration of the MRI apparatus 100 according to the embodiment has been described above. Based on such a configuration, the MRI apparatus 100 according to the embodiment executes non-contrast CEST imaging, map imaging, and contrast CEST imaging, calculates peaks of chemical shifts corresponding to a plurality of substances using MR data collected in each imaging, and determines a state quantity based on the plurality of peaks and a reference MR signal (hereinafter referred to as state quantity determination processing). Hereinafter, the procedure regarding the state quantity determination processing will be described with reference to FIG. 8. FIG. 8 is a flowchart showing an example of the procedure of the state quantity determination processing.

[0053] Hereinafter, for the sake of specific description, it is assumed that the static magnetic field strength is 3T, the predetermined frequency range is 1 ppm, and the contrast agent is iopamidol. At this time, the two CEST substances correspond to two amide groups corresponding to a chemical shift of 4.2 ppm and one amide group corresponding to a chemical shift of 5.6 ppm. The frequency of the saturation pulse of water corresponding to 0 ppm, that is, the center frequency, is 128 MHz. Also, it is assumed that the sequence information regarding map imaging is preset. Also, the sequence information regarding non-contrast CEST imaging and contrast CEST imaging is preset except for the frequencies of a plurality of saturation pulses. Since known methods are applicable for the setting of the above sequence information, the description thereof is omitted. Also, in the state quantity determination processing, non-contrast CEST imaging, map imaging, and contrast CEST imaging image the same object. That is, the imaging target sites in non-contrast CEST imaging, map imaging, and contrast CEST imaging are the same.

[0054] The stimulation mechanism 160 is controlled by the computer 130. By applying a stimulation to the contrast agent nanoparticles administered to the subject P and accumulated in the target tissue due to the EPT effect, the stimulation mechanism 160 causes the contrast agent nanoparticles to disintegrate. Since the contrast agent flows out from the disintegrated contrast agent nanoparticles, it becomes possible to acquire a contrast MR image. The stimulation mechanism 160 corresponds to the stimulation application unit.

[0055] <State quantity determination process> (Step S201) In response to a user instruction via the input device 141, the sequence control circuit 120 performs positioning imaging and map imaging on the subject P. The positioning imaging includes locator imaging and high-speed imaging for ROI setting. Also, the map imaging may include B1 shim imaging or the like. Note that, in this step, other pre-imaging may be performed. The acquisition function 121 acquires MR data (hereinafter referred to as positioning MR data) by the positioning imaging. Also, the acquisition function 121 acquires map MR data by the map imaging.

[0056] (Step S202) The image generation function 134 generates a positioning image based on the positioning MR data. The control function 133 displays the positioning image, also referred to as the locator image, on the display 143. The image generation function 134 generates a B 0 map based on the map MR data. The control function 133 stores the B 0 map in the storage circuit 132.

[0057] (Step S203) Based on a user instruction via the input device 141, the acquisition function 136 acquires the ROI in the locator image and information regarding the contrast agent. By this step, the position of the ROI related to the determination of the state quantity and a plurality of chemical shifts corresponding to a plurality of CEST substances in the contrast agent are acquired. The acquisition function 136 associates the position of the ROI and the plurality of chemical shifts and stores them in the storage circuit 132. Specifically, the acquisition function 136 acquires two chemical shifts (4.2 ppm and 5.6 ppm) in iopamidol.

[0058] (Step S204) The determination function 138 is the B in the ROI 0Based on the value, a predetermined frequency range, and two chemical shifts corresponding to two CEST substances in the contrast agent, determine the frequency band (the frequencies of multiple saturation pulses) used for CEST imaging. Specifically, the determination function 138 determines the B 0 value corresponding to the position of the ROI based on the stored position of the ROI and the B 0 map. The determination function 138 reads out the predetermined frequency range from the storage circuit 132. The determination function 138 determines the frequency band for multiple saturation pulses used for CEST imaging based on the read predetermined frequency range and the two chemical shifts corresponding to the two CEST substances. The determination function 138 determines the frequencies of multiple saturation pulses based on the determined B 0 value and the frequency band. The determination function 138 determines the reference frequency outside the frequency band based on the two chemical shifts corresponding to the two CEST substances in the contrast agent. The determination function 138 causes the storage circuit 132 to store the reference frequency and the determined frequencies of multiple saturation pulses.

[0059] (Step S205) In response to a user instruction via the input device 141, the sequence control circuit 120 performs non-contrast CEST imaging on the subject P. The acquisition function 121 acquires a first magnetic resonance signal group by performing non-contrast CEST imaging. At this time, the acquisition function 121 also acquires a reference MR signal corresponding to the reference frequency. The acquisition function 121 causes the storage circuit 132 to store the first magnetic resonance signal group and the reference MR signal. The image generation function 134 generates a plurality of non-contrast MR images based on the first magnetic resonance signal group. The image generation function 134 causes the storage circuit 132 to store the plurality of non-contrast MR images.

[0060] (Step S206) After injecting the contrast agent nanoparticles into the subject P, the sequence control circuit 120 performs contrast CEST imaging on the subject P in response to an instruction from the user via the input device 141. The acquisition function 121 acquires a second magnetic resonance signal group by performing the contrast CEST imaging. At this time, the acquisition function 121 also acquires a reference MR signal corresponding to the reference frequency. The acquisition function 121 stores the second magnetic resonance signal group and the reference MR signal in the storage circuit 132. The image generation function 134 generates a plurality of contrast MR images based on the second magnetic resonance signal group. The image generation function 134 stores the plurality of contrast MR images in the storage circuit 132.

[0061] In step S206, as shown in FIG. 1, (A) contrast agent nanoparticles (also simply referred to as "nanoparticles") are administered (injected), (B) the accumulation of the nanoparticles in the target tissue is monitored, (C) the nanoparticles are given a dissolution stimulus to cause them to disintegrate, and (D) CEST imaging is performed.

[0062] The contrast agent nanoparticles injected into the subject P accumulate in the target tissue due to the EPR effect. When the accumulation of the contrast agent nanoparticles in the target tissue is monitored and sufficiently accumulated for imaging, the contrast agent nanoparticles are caused to disintegrate by applying a stimulus to the contrast agent nanoparticles from the stimulation mechanism 160, and the encapsulated contrast agent is released. The monitoring of the accumulation of the contrast agent nanoparticles in the target organ is not particularly limited, but can be performed by magnetic resonance, X-ray, visible light, or the like. The stimulus applied to the contrast agent nanoparticles from the stimulation mechanism is not particularly limited as long as it can cause the contrast agent nanoparticles to disintegrate, but an electromagnetic field, an electric field, a magnetic field, heat, ultrasonic waves, or the like can be used.

[0063] FIG. 2 is a flowchart showing an example of the process from administering (injecting) the contrast agent nanoparticles to the subject P until CEST imaging is performed. Step S11: Administer (inject) the contrast agent nanoparticles to the subject P. Step S12: The contrast agent nanoparticles accumulate in the target tissue by the EPR effect. Step S13: Monitor the accumulation of the contrast agent nanoparticles in the target tissue. Step S14: If there is a change in the target tissue (target site), execute Step 15; if there is no change, return to Step 13 and continue monitoring the accumulation of the contrast agent nanoparticles. Step S15: Apply a dissolution stimulus to the accumulated contrast agent nanoparticles to dissolve them and release the encapsulated contrast agent. Step S16: Perform CEST imaging.

[0064] In one aspect, the monitoring of the accumulation of the contrast agent nanoparticles in the target tissue is performed using MRI. The outer surface of the contrast agent nanoparticles is preferably modified with metal ions that significantly change the relaxation time to facilitate the monitoring. Such metal ions are preferably alkali metal ions such as lithium ions, sodium ions, or potassium ions. As the monitoring method, it is preferable to continuously capture the change in the relaxation time by fast imaging. To dissolve the contrast agent nanoparticles and release the encapsulated contrast agent, means adapted to the design of the nanoparticles, such as irradiating the contrast agent nanoparticles accumulated in the target tissue with an RF pulse in MRI or irradiating them with heat, are used. In this aspect, by acquiring in advance the concentration of the contrast agent (CEST substance) encapsulated in the contrast agent nanoparticles, it is possible to estimate the concentration of the contrast agent (CEST substance) released from the contrast agent nanoparticles in the target tissue from the accumulation amount of the contrast agent nanoparticles and the dissolution efficiency by the dissolution stimulus.

[0065] In another aspect, the monitoring of the accumulation of the contrast agent nanoparticles in the target tissue is performed using an ultrasonic imaging device. The outer surface of the contrast agent nanoparticles is preferably surface-modified such that the reflectivity of (ultra) sound waves is different in order to facilitate monitoring. Examples of such surface modifications include modifications with metal nanoparticles, polymer nanoparticles, and the like. As a monitoring method, it is preferable to capture changes in the reflectivity of (ultra) sound waves. To dissolve the contrast agent nanoparticles and release the encapsulated contrast agent, means adapted to the design of the nanoparticles, such as irradiating the contrast agent nanoparticles accumulated in the target tissue with ultrasonic waves, electromagnetic waves, ultraviolet (UV) rays, infrared (IR) rays, etc., are used. In an aspect, by previously obtaining the concentration of the contrast agent (CEST substance) encapsulated in the contrast agent nanoparticles, it is possible to estimate the concentration of the contrast agent (CEST substance) released from the contrast agent nanoparticles in the target tissue from the accumulation amount of the contrast agent nanoparticles and the dissolution efficiency due to the dissolution stimulation.

[0066] In yet another aspect, the monitoring of the accumulation of the contrast agent nanoparticles in the target tissue is performed using a radiation imaging device. The outer surface of the contrast agent nanoparticles is preferably surface-modified such that the transmittance of radiation is different in order to facilitate monitoring. Examples of such surface modifications include modifications with metal nanoparticles. As a monitoring method, it is preferable to capture changes in the reflectivity of (ultra) sound waves. To dissolve the contrast agent nanoparticles and release the encapsulated contrast agent, means adapted to the design of the nanoparticles, such as irradiating the contrast agent nanoparticles accumulated in the target tissue with ultrasonic waves, electromagnetic waves, ultraviolet (UV) rays, infrared (IR) rays, etc., are used. In an aspect, by previously obtaining the concentration of the contrast agent (CEST substance) encapsulated in the contrast agent nanoparticles, it is possible to estimate the concentration of the contrast agent (CEST substance) released from the contrast agent nanoparticles in the target tissue from the accumulation amount of the contrast agent nanoparticles and the dissolution efficiency due to the dissolution stimulation.

[0067] During the period until the contrast agent nanoparticles accumulate in the target tissue (for example, about 15 to 60 minutes), the sequence control circuit 120 may perform various imaging. For example, during the period from immediately after the injection of the contrast agent nanoparticles into the subject P until before the return of the contrast CEST imaging, the sequence control circuit 120 may perform positioning imaging according to the inspection order, re-imaging of map imaging, imaging for obtaining a T1-weighted image, imaging for obtaining a T2-weighted image, EPI, or any other imaging.

[0068] (Step S207) The image generation function 134 generates a non-contrast Z spectrum (first Z spectrum) regarding the ROI by applying B 0 correction based on a plurality of non-contrast MR images and a B 0 map. The image generation function 134 stores the generated non-contrast Z spectrum in the storage circuit 132.

[0069] FIG. 9 is a diagram showing an example of a non-contrast Z spectrum NCZ. The distribution of signal values included in the dotted frame NCSD shown in FIG. 9 indicates the distribution of the signal of water with respect to the frequency (ppm) of the saturation pulse in non-contrast. In addition, the non-contrast Z spectrum NCZ shows a reference MR signal BS with respect to a reference frequency BF smaller than -10 ppm.

[0070] (Step S208) The image generation function 134 generates a contrast Z spectrum (second Z spectrum) regarding the ROI by applying B 0 correction based on a plurality of contrast MR images and a B 0 map. The image generation function 134 stores the generated contrast Z spectrum in the storage circuit 132.

[0071] FIG. 10 is a diagram showing an example of a contrast Z spectrum CZ. The distribution of signal values included in the dotted frame CSD shown in FIG. 10 shows the distribution of the signal of water with respect to the frequency (ppm) of the saturation pulse in the contrast Z spectrum CZ. In addition, the contrast Z spectrum CZ shows a reference MR signal BS with respect to a reference frequency BF smaller than -10 ppm. Also, 0 ppm B 0 in the contrast Z spectrum CZ 0 corresponds to the frequency determined by the correction. Note that when the collection of the reference MR signal BS is collected in either non-contrast CEST imaging or contrast CEST imaging, the reference MR signal BS is, for example, not displayed in the non-contrast Z spectrum NCZ and the contrast Z spectrum CZ.

[0072] (Step S209) The computing function 140 differentiates the contrast Z spectrum CZ and the non-contrast Z spectrum NCZ to generate a difference spectrum. Specifically, the computing function 140 generates a difference spectrum by differentiating the contrast Z spectrum CZ from the non-contrast Z spectrum NCZ. The computing function 140 causes the generated difference Z spectrum to be stored in the storage circuit 132.

[0073] FIG. 11 is a diagram showing an example of a difference spectrum DS. As shown in FIG. 11, the difference spectrum DS includes the distribution of signal values of the signal of water having two chemical shifts (4.2 ppm and 5.6 ppm) in iopamidol as peaks.

[0074] (Step S210) The detection function 142 detects two peaks corresponding to two CEST substances based on the difference spectrum DS. For example, the detection function 142 performs function fitting or estimation of the profile of the distribution of the signal values in the difference spectrum DS. Thereby, the detection function 142 detects two peaks corresponding to two CEST substances in the difference spectrum DS. The detection function 142 causes the two detected peaks to be stored in the storage circuit 132.

[0075] FIG. 12 is a diagram showing an example in which function fitting is performed on the differential spectrum DS. As shown in FIG. 12, by applying fitting processing to the differential spectrum DS using the function indicating 4.2 ppm and the function indicating 5.6 ppm, the detection function 142 detects peaks at 4.2 ppm and 5.6 ppm.

[0076] Note that the detection of peaks is not limited to the above. For example, when a plurality of differential spectra are generated, the detection function 142 calculates the ppm related to a plurality of peaks (hereinafter referred to as peak ppm), the ppm located in the middle of adjacent peak ppm (hereinafter referred to as intermediate ppm), and the ppm at two positions separated by the distance between adjacent peak ppm along the direction opposite to the direction from each of the two peak ppm toward the intermediate ppm (hereinafter referred to as separated ppm). That is, the detection function 142 integrates a plurality of signal values at each of the five points (two peak ppm, intermediate ppm, two separated ppm). That is, the detection function 142 averages the plurality of signal values at each of the five points in the plurality of differential spectra.

[0077] FIG. 13 is a diagram showing an example of the integrated differential spectrum SDS. When the contrast agent contains two CEST substances with two peaks respectively, the integrated differential spectrum has five points as shown in FIG. 13. The detection function 142 estimates the signal values of the two peaks for the integrated differential spectrum SDS shown in FIG. 13. For example, the detection function 142 detects peaks at 4.2 ppm and 5.6 ppm by performing function fitting or profiling the distribution at that point. The profiling is, for example, fitting two approximate expressions corresponding to the peaks of the two CEST substances with the signal values at the two peak ppm (4.2 ppm and 5.6 ppm) as the maximum values, the intermediate ppm (4.9 ppm) as the minimum value, and the two separated ppm (2.8 ppm, 7.0 ppm) as the initial values near the contact points on the horizontal axis to detect the two peaks.

[0078] (Step S211) The computing function 140 calculates the state quantity in the ROI based on the two detected peaks and the reference MR signal. The computing function 140 causes the memory circuit 132 to store the calculated state quantity.

[0079] (Step S212) The control function 133 causes the calculated state quantity to be displayed on the display 143.

[0080] The MRI apparatus 100 according to the above-described embodiment acquires information regarding a contrast agent containing a plurality of substances having different chemical shifts, determines a frequency band related to the decrease in the magnetic resonance signal due to the chemical shift based on the acquired information, and, before contrast imaging with the contrast agent, collects a first magnetic resonance signal group while changing the conditions of the saturation pulse with respect to the determined frequency band by CEST (Chemical Exchange Saturation Transfer) imaging, and, after contrast imaging with the contrast agent, collects a second magnetic resonance signal group while changing the conditions of the saturation pulse with respect to the frequency band by CEST imaging, calculates the difference between a first Z spectrum generated based on the first magnetic resonance signal group and a second Z spectrum generated based on the second magnetic resonance signal group, and detects a plurality of peaks corresponding to the chemical shifts of the plurality of substances and indicating a decrease in the magnetic resonance signal based on the calculated difference.

[0081] In the MRI apparatus 100 according to the present embodiment, the first magnetic resonance signal group and the second magnetic resonance signal group correspond to a plurality of MR signals collected in a local frequency band as compared with the frequency band of a conventional saturation pulse. Further, in the MRI apparatus 100 according to the present embodiment, the first Z spectrum and the second Z spectrum correspond to local Z spectra as compared with a conventional Z spectrum (full spectrum).

[0082] Further, the MRI apparatus 100 according to the embodiment generates B before the execution of the CEST imaging. 0Further use the map to determine the frequency band. Also, the MRI apparatus 100 according to the embodiment detects a plurality of peaks by function fitting for the distribution of signal values in the calculated difference or estimation of the profile of the distribution. Further, the MRI apparatus 100 according to the embodiment determines, based on the acquired information, a frequency outside the determined frequency band and not involved in the decrease in the magnetic resonance signal due to the chemical shift, and uses the determined frequency as a saturation pulse or collects a reference MR signal serving as a reference for the first Z spectrum and the second Z spectrum without using a saturation pulse. The first Z spectrum is generated based on the first magnetic resonance signal group and the reference MR signal, and the second Z spectrum is generated based on the second magnetic resonance signal group and the reference MR signal.

[0083] Also, the MRI apparatus 100 according to the embodiment calculates a state quantity in the imaging region regarding the first Z spectrum and the second Z spectrum based on the detected plurality of peaks and the reference MR signal. In the MRI apparatus 100 according to the embodiment, the calculated state quantity is the temperature or pH in the imaging region of the East Asian technique.

[0084] From these, according to the MRI apparatus 100 according to the embodiment, regarding the detection of the peaks of the decrease in the signal values regarding a plurality of CEST substances, it is possible to realize a fitting method that reduces the influence of unconsidered parameters in the living body (such as the initial value of the fitting function for each site) and also reduces the imaging time and initial conditions. Thereby, according to the MRI apparatus 100 according to the embodiment, by significantly reducing the time for calculating the signal value of the peak and the number of data points required for the Z spectrum used for the calculation, the imaging time can be reduced while improving the accuracy of the data regarding the peak.

[0085] FIG. 14 is a diagram showing an example of the effects of this embodiment. In the conventional CV technique that acquires a full spectrum at intervals of 0.1 ppm within the frequency range of -10 ppm to 10 ppm of the saturation pulse, 201 images are acquired. At this time, fitting FT is performed using five approximate formulas for the Z spectrum CZS in the conventional CV. On the other hand, in this embodiment EM, it is possible to collect images in (2n + 1 + 1) numbers centered on the chemical shift of each of the two CEST substances. For example, if n = 10, a total of 88 images are collected before and after the contrast agent. Therefore, according to the MRI apparatus 100 according to this embodiment, imaging can be performed in about half or less time compared to the conventional method.

[0086] As shown in FIG. 14, when iopamidol is used as the contrast agent, centering on the chemical shifts (4.2 ppm and 5.6 ppm) of each of the two CEST substances, including the reference frequency, the number of CEST imaging times is 72 points (36 points + 36 points) in total including before and after the contrast agent. That is, according to the MRI apparatus 100 according to this embodiment, the number of imaging times is reduced to half or less compared to the conventional method. Further, as shown in FIG. 14, in the fitting FT for the difference spectrum DS generated by the difference Diff between the non-contrast Z spectrum NCZ and the contrast Z spectrum CZ, the number of boundary conditions and fitting curves is reduced from 5 to 2 compared to the conventional method, and the fitting accuracy can be improved.

[0087] From the above, according to the MRI apparatus 100 according to the embodiment, it is possible to reduce the imaging time and the initial conditions (boundary conditions) required for fitting, and to obtain a high-precision peak signal value in a shorter time than the conventional method. Therefore, the state quantity in the ROI can be calculated with high precision and in a short time.

[0088] When realizing the technical idea in the embodiment by the chemical shift peak detection method, the chemical shift peak detection method acquires information about a contrast agent containing a plurality of substances (CEST substances) with different chemical shifts, and based on the acquired information, determines a frequency band related to the decrease in the magnetic resonance signal due to the chemical shift. Before contrast imaging with the contrast agent, by CEST (Chemical Exchange Saturation Transfer) imaging, a first magnetic resonance signal group is collected while changing the conditions of the saturation pulse with respect to the frequency band. After contrast imaging with the contrast agent, by CEST imaging, a second magnetic resonance signal group is collected while changing the conditions of the saturation pulse with respect to the frequency band. The difference between a first Z spectrum generated based on the first magnetic resonance signal group and a second Z spectrum generated based on the second magnetic resonance signal group is calculated, and based on the calculated difference, a plurality of peaks corresponding to the plurality of substances and indicating the decrease in the magnetic resonance signal are detected.

[0089] The contrast agent containing CEST substances is administered to the subject to be imaged in the form of nanoparticles (contrast agent nanoparticles) encapsulating the contrast agent before the start of contrast imaging. The contrast agent nanoparticles administered to the subject to be imaged accumulate at the imaging target site such as a tumor by the EPR (Enhanced Permeability and Retention) effect in the body of the subject to be imaged. The accumulation of the contrast agent nanoparticles at the imaging target site is monitored, and after the accumulation amount of the CEST substance becomes sufficient for CEST imaging, the contrast agent nanoparticles are stimulated to dissolve the nanoparticles. Then, CEST imaging is performed.

[0090] The chemical peak shift detection method according to the embodiment applies a dissolution stimulus to the contrast agent nanoparticles accumulated in the imaging region of the subject, and before the contrast by the contrast agent nanoparticles, a first magnetic resonance signal group is collected by CEST imaging while changing the conditions of the saturation pulse. After the contrast by the contrast agent nanoparticles and after applying the dissolution stimulus to the contrast agent nanoparticles, a second magnetic resonance signal group is collected by the CEST imaging while changing the conditions of the saturation pulse. A difference between a first Z spectrum generated based on the first magnetic resonance signal group and a second Z spectrum generated based on the second magnetic resonance signal group is calculated, and based on the difference, a plurality of peaks indicating a decrease in the magnetic resonance signal due to the chemical shift are detected. Since the procedure and effect of the state quantity determination process including the processing procedure of the chemical shift peak detection method are the same as those of the embodiment, the description thereof is omitted.

[0091] According to at least one of the embodiments described above, the imaging time can be shortened and the detection accuracy of the chemical shift peak can be improved.

[0092] Although several embodiments have been described, these embodiments are presented as examples and are not intended to limit the scope of the invention. These embodiments can be implemented in various other forms, and various omissions, replacements, changes, and combinations of the embodiments can be made without departing from the gist of the invention. These embodiments and their modifications are included in the scope and gist of the invention, and are also included in the invention described in the claims and the equivalent scope thereof.

Explanation of Reference Numerals

[0093] 100 Magnetic resonance imaging apparatus 101 Static magnetic field magnet 102 Static magnetic field power supply 103 Gradient magnetic field coil 104 Gradient magnetic field power supply 105 Bed 105a Top plate 106 Bed control circuit 107 Transmission coil 108 Transmission circuit 109 Receiving coil 110 Receiving circuit 120 Sequence control circuit 121 Collection function 130 Computer 131 Interface function 132 Memory circuit 133 Control function 134 Image generation function 136 Acquisition function 138 Decision function 140 Calculation function 141 Input device 142 Detection function 143 Display 144 Detection function 146 Acquisition function 150 Processing circuit 160 Stimulation mechanism 1101 Blood vessels near the tumor 1102 Blood vessels of normal tissue 1103 Tumor 1104 Normal tissue 1201 Nanoparticles 1202 CEST substance P Subject

Claims

1. A stimulation unit that applies a dissolution stimulation to the contrast agent nanoparticles accumulated in an imaging region after injecting the contrast agent nanoparticles into a subject; Before contrast imaging with the contrast agent nanoparticles, a collection unit that collects a first magnetic resonance signal group while changing the conditions of a saturation pulse by CEST imaging, and after contrast imaging with the contrast agent nanoparticles and after applying the dissolution stimulation by the stimulation unit, the collection unit collects a second magnetic resonance signal group while changing the conditions of the saturation pulse by the CEST imaging; A calculation unit that calculates the difference between a first Z spectrum generated based on the first magnetic resonance signal group and a second Z spectrum generated based on the second magnetic resonance signal group; A detection unit that detects a plurality of peaks indicating a decrease in magnetic resonance signal due to chemical shift based on the difference A magnetic resonance imaging apparatus comprising the above.

2. Furthermore, An acquisition unit that acquires information regarding a contrast agent containing a plurality of substances having different chemical shifts; A determination unit that determines a frequency band related to a decrease in magnetic resonance signal due to the chemical shift based on the information The magnetic resonance imaging apparatus according to claim 1, comprising the above.

3. The determination unit further uses the B ０ map generated before the execution of the CEST imaging to determine the frequency band, and the magnetic resonance imaging apparatus according to claim 2.

4. The detection unit detects the plurality of peaks by function fitting to the distribution of signal values in the difference or estimation of the outline of the distribution. The magnetic resonance imaging apparatus according to any one of claims 1 to 3.

5. The determination unit determines a frequency outside the frequency band and not involved in the decrease in the magnetic resonance signal due to the chemical shift based on the information, The collection unit uses the determined frequency as a saturation pulse or without using the saturation pulse to collect a reference MR signal serving as a reference for the first Z spectrum and the second Z spectrum, The first Z spectrum is generated based on the first magnetic resonance signal group and the reference MR signal, The second Z spectrum is generated based on the second magnetic resonance signal group and the reference MR signal. The magnetic resonance imaging apparatus according to claim 2 or 3.

6. The calculation unit calculates a state quantity in an imaging region related to the first Z spectrum and the second Z spectrum based on the plurality of peaks and the reference MR signal. The magnetic resonance imaging apparatus according to claim 5.

7. The magnetic resonance imaging apparatus according to claim 6, wherein the state quantity is temperature or pH in the imaging region.

8. Apply a dissolution stimulus to the contrast agent nanoparticles accumulated in the imaging region of the subject, Before contrast imaging with the contrast agent nanoparticles, collect a first magnetic resonance signal group by CEST imaging while changing the conditions of the saturation pulse, After contrast imaging with the contrast agent nanoparticles and after applying a dissolution stimulus to the contrast agent nanoparticles, collect a second magnetic resonance signal group by the CEST imaging while changing the conditions of the saturation pulse, Calculate the difference between a first Z-spectrum generated based on the first magnetic resonance signal group and a second Z-spectrum generated based on the second magnetic resonance signal group, Detect a plurality of peaks indicating a decrease in the magnetic resonance signal due to chemical shift based on the difference. A chemical shift peak detection method comprising the steps of:

9. Before applying a dissolution stimulus to the contrast agent nanoparticles, further obtain information on a contrast agent containing a plurality of substances having different chemical shifts, and based on the information, determine a frequency band related to a decrease in the magnetic resonance signal due to the chemical shift. The chemical shift peak detection method according to claim 8, comprising the step of:

10. After collecting the first magnetic resonance signal group, further monitor the accumulation of the contrast agent nanoparticles formed by encapsulating a contrast agent containing a plurality of substances having different chemical shifts in stimulus-responsive nanoparticles in the target tissue of the subject. When the contrast agent nanoparticles have accumulated in the target tissue to such an extent that CEST imaging can be sufficiently performed, apply a dissolution stimulus to the contrast agent nanoparticles to release the encapsulated contrast agent and perform contrast imaging of the target tissue. The chemical shift peak detection method according to claim 9, comprising the step of:

11. The method for detecting a chemical shift peak according to any one of claims 8 to 10, wherein the monitoring of the accumulation of the contrast agent nanoparticles in the target tissue is performed using a magnetic resonance imaging apparatus, a radiation imaging apparatus, or an ultrasonic imaging apparatus.

12. The method for detecting a chemical shift peak according to any one of claims 8 to 10, wherein the dissolution stimulus for the contrast agent nanoparticles is RF pulse irradiation, electromagnetic wave irradiation, ultrasonic irradiation, radiation irradiation, ultraviolet irradiation, infrared irradiation, or heat irradiation.

13. A contrast agent nanoparticle formed by encapsulating a contrast agent containing a plurality of substances having different chemical shifts in stimulus-responsive nanoparticles.

14. The contrast agent nanoparticle according to claim 13, wherein the contrast agent is iopamidol.

15. The contrast agent nanoparticle according to claim 13 or 14, wherein the stimulus-responsive nanoparticle is a liposome.

16. The contrast agent nanoparticle according to claim 15, wherein the outer surface of the liposome is modified with a polymer, metal, metal complex, or metal ion.

17. The contrast agent nanoparticle according to claim 13 or 14, for use in a magnetic resonance imaging apparatus according to any one of claims 1 to 3.

18. The contrast agent nanoparticle according to claim 13 or 14, for use in a chemical shift peak detection method according to any one of claims 8 to 10.

Images