DETECTION METHOD, DETECTION SYSTEM, PROGRAM, AND RECORDING MEDIUM

Abstract

An information processing device (9) of the detection system (100) acquires a first phase of a first signal of a specific frequency extracted from a magnetic signal when a first magnetic particle is placed in a target area, and acquires a second phase of a second signal of a specific frequency extracted from a magnetic signal when a second magnetic particle is placed in the target area. At the specific frequency, a relaxation time of a magnetic moment of the second magnetic particle is different from a relaxation time of a magnetic moment of the first magnetic particle. The information processing device (9) further acquires a third signal of a specific frequency extracted from a magnetic signal when a test object (6) including the first magnetic particle and the second magnetic particle is placed in the target area. The information processing device (9) uses the first phase and the second phase to discriminate a target component of the target particle from among the first magnetic particle and the second magnetic particle from the third signal.

Description

[Technical field]

[0001] The present disclosure relates to a detection method, a detection system, a program, and a recording medium for detecting magnetic particles. [Background technology]

[0002] Conventionally, a detection device for detecting magnetic particles is known, which includes an AC magnetic field applicator and a DC magnetic field generator. Only magnetic particles present in the zero magnetic field region generated by the DC magnetic field generator undergo magnetization fluctuation due to the AC excitation magnetic field applied by the AC magnetic field applicator. Therefore, by scanning the zero magnetic field region in the test object, distribution information of magnetic particles in the test object can be obtained.

[0003] Magnetic signals that indicate magnetization fluctuations of magnetic particles contain signals of various frequencies. Signals at the same frequency as the excitation magnetic field are a mixture of signals caused by magnetic particles and signals excited by the excitation magnetic field. Therefore, the signal-to-noise ratio of signals at the same frequency as the excitation magnetic field is low. Therefore, harmonic signals with a high signal-to-noise ratio are usually used.

[0004] Known methods for extracting harmonic signals from magnetic signals include a method using a frequency filter, a method using a fast Fourier transform, and a method using synchronous detection with a lock-in amplifier. JP 2003-199767 A (Patent Document 1) discloses a method using a frequency filter. "Gleich, B, Weizenecker, J, 'Tomographic imaging using the nonlinear response of magnetic particles', Nature, Vol. 435, 2005, pp. 1214-1217" (Non-Patent Document 1) discloses a method using a fast Fourier transform. "Kenya Murase et al, 'Development of a system for magnetic particle imaging using neodymium magnets and gradiometer', Japanese Journal of Applied Physics, 53, 067001 (2014)" (Non-Patent Document 2) discloses a method using synchronous detection with a lock-in amplifier. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2003-199767 A [Non-patent literature]

[0006] [Non-Patent Document 1] Gleich, B, Weizenecker, J, "Tomographic imaging using the nonlinear response of magnetic particles", nature, vol. 435, 2005, pp. 1214-1217 [Non-Patent Document 2] Kenya Murase et al, “Development of a system for magnetic particle imaging using neodymium magnets and gradiometer”, Japanese Journal of Applied Physics, 53, 067001 (2014) Summary of the Invention [Problem to be solved by the invention]

[0007] The techniques disclosed in Patent Document 1, Non-Patent Document 1, and Non-Patent Document 2 are premised on obtaining distribution information of one type of magnetic particle. Therefore, the techniques disclosed in Patent Document 1, Non-Patent Document 1, and Non-Patent Document 2 cannot be applied to discriminating one component of two magnetic particles.

[0008] The present disclosure has been made in consideration of the above-mentioned problems, and aims to provide a detection method, detection system, program, and recording medium capable of discriminating one component of two magnetic particles. [Means for solving the problem]

[0009] A detection method according to an aspect of the present disclosure detects magnetic particles using an alternating excitation magnetic field. The detection method includes acquiring a first phase of a first signal of a specific frequency generated in response to a change in the magnetic moment of a first magnetic particle when the excitation magnetic field is applied, and acquiring a second phase of a second signal of a specific frequency generated in response to a change in the magnetic moment of a second magnetic particle when the excitation magnetic field is applied. At the specific frequency, the relaxation time of the magnetic moment of the second magnetic particle is different from the relaxation time of the magnetic moment of the first magnetic particle. The detection method further includes acquiring a third signal of a specific frequency generated in response to a change in the magnetic moment of a target region including the first magnetic particle and the second magnetic particle when the excitation magnetic field is applied, and discriminating a target component of the target particle from the third signal using the first phase and the second phase.

[0010] A detection system according to an aspect of the present disclosure includes an excitation magnetic field applicator that applies an alternating excitation magnetic field to a target region, a magnetic sensor that detects a magnetic signal indicative of a change in the magnetic moment of the target region, and a processor. The processor acquires a first phase of a first signal of a specific frequency extracted from the magnetic signal when a first magnetic particle is placed in the target region. The processor acquires a second phase of a second signal of a specific frequency extracted from the magnetic signal when a second magnetic particle is placed in the target region. At the specific frequency, the relaxation time of the magnetic moment of the second magnetic particle is different from the relaxation time of the magnetic moment of the first magnetic particle. The processor further acquires a third signal of a specific frequency extracted from the magnetic signal when an object to be inspected including the first magnetic particle and the second magnetic particle is placed in the target region. The processor uses the first phase and the second phase to discriminate a target component of the target particle from the third signal, which is the first magnetic particle and the second magnetic particle.

[0011] A program according to an aspect of the present disclosure causes a computer to execute the above detection method.A computer-readable recording medium according to an aspect of the present disclosure records the above program. Effect of the Invention

[0012] The detection method, detection system, program, and recording medium disclosed herein can distinguish one component of two magnetic particles by using a phase difference based on the difference in relaxation time of the magnetic moments of the two magnetic particles. [Brief description of the drawings]

[0013] [Figure 1] 1 is a diagram showing an example of an overall configuration of a detection system according to a first embodiment. [Diagram 2] FIG. 2 is a perspective view showing a portion of the detection system. [Diagram 3] FIG. 2 is a diagram showing magnetic particles in a test subject. [Figure 4] FIG. 2 is a diagram showing two types of magnetic particles according to the first embodiment. [Diagram 5]FIG. 1 is a diagram showing the configuration of a lock-in amplifier. [Figure 6] FIG. 2 illustrates an example of a hardware configuration of an information processing device. [Figure 7] 13 is a flowchart showing an example of a process flow of the advance preparation phase. [Figure 8] FIG. 11 is a diagram illustrating the process of step S2. [Figure 9] FIG. 11 is a diagram illustrating the process of step S5. [Figure 10] 13 is a flowchart showing an example of a process flow of a measurement phase. [Figure 11] FIG. 11 is a diagram for explaining a process in a measurement phase. [Figure 12] 13 is a flowchart showing an example of a flow of spatial distribution imaging. [Figure 13] 2 is a diagram showing an example of a user interface screen provided by the detection system shown in FIG. 1. [Figure 14] FIG. 13 is a diagram showing two types of magnetic particles detected by a detection system according to a fifth embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the drawings. In addition, the same or corresponding parts in the drawings are given the same reference numerals, and the description thereof will not be repeated. The embodiments and modifications described below may be appropriately and selectively combined.

[0015] Embodiment 1 (Overall configuration of the detection system) Fig. 1 is a diagram showing an example of the overall configuration of a detection system according to embodiment 1. The detection system 100 shown in Fig. 1 includes an excitation magnetic field applicator 1, a zero magnetic field generator 2, a magnetic sensor 3, a lock-in amplifier 4, a first power supply 7, a second power supply 8a, a third power supply 8b, and an information processing device 9.

[0016] The excitation magnetic field applicator 1 applies an alternating excitation magnetic field to an area in which the subject 6 is placed (hereinafter referred to as the "measurement area 5"). The subject 6 may include, but is not limited to, a human body, an animal, etc. Specifically, the excitation magnetic field applicator 1 is composed of a coil connected to a first power source 7. An excitation magnetic field is applied to the measurement area 5 by passing a current from the first power source 7 to the excitation magnetic field applicator 1.

[0017] The zero magnetic field generator 2 forms a zero magnetic field region in the measurement area 5. Specifically, the zero magnetic field generator 2 includes a pair of electromagnets 2a, 2b arranged facing each other so that the directions of magnetization are opposite to each other. The electromagnets 2a, 2b are connected to a second power source 8a and a third power source 8b, respectively. A zero magnetic field region is generated by passing a current from the second power source 8a and the third power source 8b to the electromagnets 2a, 2b, respectively.

[0018] In this embodiment, the zero magnetic field generator 2 includes electromagnets 2a and 2b, but the zero magnetic field generator 2 may use two permanent magnets arranged opposite each other or a combination of a permanent magnet and an electromagnet instead of the electromagnets 2a and 2b. When the zero magnetic field region is formed by two permanent magnets, the second power supply 8a and the third power supply 8b are omitted.

[0019] The magnetic sensor 3 detects magnetic signals indicative of changes in the magnetic moment of magnetic particles present in the zero magnetic field region when an excitation magnetic field is applied.

[0020] The lock-in amplifier 4 extracts a signal of a specific frequency from the magnetic signal. The specific frequency is the frequency of a reference signal generated by the first power supply 7. The reference signal is a signal of a higher harmonic (m×f0) (m is an integer equal to or greater than 2) of a fundamental wave f0 having the same frequency as the excitation magnetic field. In other words, the specific frequency is a frequency m times the frequency of the excitation magnetic field. The signal extracted by the lock-in amplifier 4 is output to the information processing device 9.

[0021] The information processing device 9 is connected to each unit of the detection system 100 via a bus. The information processing device 9 executes various information processing for controlling the operation of the detection system 100. The information processing device 9 detects magnetic particles present in the zero magnetic field region based on the signal extracted by the lock-in amplifier 4.

[0022] (Zero magnetic field region) Fig. 2 is a perspective view showing a part of the detection system. In the example shown in Fig. 2, a linear zero magnetic field region (Field Free Line (FFL)) 30 is generated by a pair of electromagnets 2a and 2b included in the zero magnetic field generator 2. However, in this embodiment, the shape of the zero magnetic field region 30 is not limited to a linear shape. For example, the zero magnetic field region 30 may be a point-like zero magnetic field region (Field Free Point (FFP)).

[0023] The zero magnetic field region 30 may be scanned in the subject 6. Specifically, the position and direction of the zero magnetic field region 30 are scanned. The position of the zero magnetic field region 30 is represented, for example, by a position on an axis 70 of a coordinate system set in the detection system 100 (hereinafter referred to as a "scan position"). The direction of the zero magnetic field region 30 is represented, for example, by an angle φ between the zero magnetic field region 30 and an axis 72 of the coordinate system set in the detection system 100. Methods for scanning the zero magnetic field region 30 in the subject 6 may include a method of mechanically moving the zero magnetic field generator 2, a method of changing the current balance of the electromagnets 2a and 2b, or a method of mechanically moving the subject 6.

[0024] (magnetic particles) FIG. 3 is a diagram showing magnetic particles in a test subject. As shown in FIG. 3, two types of magnetic particles 51 and 52 are administered to a test subject 6. The magnetic particles 51 are an example of a "first magnetic particle" in the present disclosure. The magnetic particles 52 are an example of a "second magnetic particle" in the present disclosure. The magnetic particles 51 and 52 are also referred to as a "first type of magnetic particle" and a "second type of magnetic particle", respectively.

[0025] When an alternating excitation magnetic field is applied to the test object 6 including the magnetic particles 51, 52, the magnetic moments of only the magnetic particles 51, 52 present in the zero magnetic field region 30 are changed by the excitation magnetic field. Therefore, the zero magnetic field region 30 corresponds to a "target region" where the magnetic sensor 3 detects changes in the magnetic moments of the magnetic particles 51, 52.

[0026] The relaxation time of the magnetic moment of magnetic particle 52 when an excitation magnetic field is applied is different from the relaxation time of the magnetic moment of magnetic particle 51 when an excitation magnetic field is applied.

[0027] Fig. 4 is a diagram showing two types of magnetic particles according to embodiment 1. As shown in Fig. 4, in embodiment 1, magnetic particles 51 and 52 have different particle sizes. When Brownian motion is not dominant in magnetic particles 51 and 52, the magnetic particles 51 and 52 have different particle sizes, and therefore the Neel relaxation times of the magnetic particles 51 and 52 are different from each other.

[0028] A probe 51a having a property of binding to a first protein is attached to the magnetic particle 51. A probe 52a having a property of binding to a second protein is attached to the magnetic particle 52. When a certain time has elapsed since the magnetic particles 51 and 52 were introduced into the test subject 6, the magnetic particles 51 and 52 bind to the first and second proteins present in the tissue 60 in the test subject 6 via the probes 51a and 52a, respectively. Therefore, by generating a zero magnetic field region 30 in the test subject 6 after the floating magnetic particles 51 and 52 are discharged from the test subject 6, a magnetic signal indicating a change in the magnetic moment of the magnetic particles 51 and 52 bound to the first and second proteins, respectively, is obtained in the zero magnetic field region 30. By discriminating each component of the magnetic particles 51 and 52 from the magnetic signal, the amount of each of the magnetic particles 51 and 52 present in the zero magnetic field region 30 can be estimated.

[0029] (Lock-in amplifier configuration) 5 is a diagram showing the configuration of a lock-in amplifier. As shown in FIG. 5, the lock-in amplifier 4 includes mixers 41 and 42, low-pass filters 43 and 44, and a computing unit 45. The lock-in amplifier 4 receives a magnetic signal V s (t), a reference signal V of a specific frequency is generated from the first power supply 7. r Receive (t).

[0030] The mixer 41 receives the magnetic signal V s (t) and the reference signal V r The mixer 41 multiplies the signal by (t) to output the X component. The low-pass filter 43 performs a filtering process on the X component output from the mixer 41.

[0031] The mixer 42 receives the magnetic signal V s (t) and the reference signal V r The mixer 42 multiplies the Y component by a signal obtained by shifting the phase of (t) by 90°, and outputs the Y component. The low-pass filter 44 performs filtering on the Y component output from the mixer 42.

[0032] The mixers 41 and 42 constitute a so-called dual-phase demodulation circuit. The dual-phase demodulation circuit demodulates a magnetic signal V s (t) and the complex reference signal V r The real part Re(Z) of the complex signal Z(t), which is a product of Z(t) and (t), is output as the X component, and the imaginary part Im(Z) of the complex signal Z(t) is output as the Y component.

[0033] Magnetic Signal V s (t) has the same speed ω as shown in the following equation (1). s Length rotated by R / (2 1 / 2 ) on the complex plane. R is the magnetic signal V s (t) is the intensity (effective value). One of the two vectors rotates clockwise and the other rotates counterclockwise.

[0034]

number

[0035] Reference signal V r (t) is a specific frequency ω that is m times the frequency of the excitation magnetic field. r The reference signal V r The phasor notation of (t) is expressed by the following equation (2). The phasor notation of the complex signal Z(t) is expressed by the following equation (3).

[0036]

number

[0037] In equation (3), the second term is the frequency (ω s +ω r ) is a high-speed rotating term. Therefore, the second term becomes 0 by the low-pass filters 43 and 44. Furthermore, ω s ω r , the first term is also set to 0 by the low-pass filters 43 and 44. Therefore, the complex signal Z(t) is expressed by the following equation (4) after passing through the low-pass filters 43 and 44. Z(t) = R e iθ =Rcosθ+iRsinθ (4) Therefore, the X component output from the low-pass filter 43 is represented by Rcosθ, which is the real part of Z(t), and the Y component output from the low-pass filter 44 is represented by Rsinθ, which is the imaginary part of Z(t).

[0038] The calculator 45 calculates R and θ according to the following equations (5) and (6) using the X and Y components output from the low-pass filters 43 and 44. R is a specific frequency ω r θ is the strength (effective value) of the signal of a specific frequency ω r Represents the phase of the signal.

[0039]

number

[0040] In this way, the lock-in amplifier 4 extracts a signal of a specific frequency generated in response to a change in the magnetic moment of the magnetic particles in the zero magnetic field region 4 from the magnetic signal received from the magnetic sensor 3, and identifies the intensity R and phase θ of the extracted signal. The lock-in amplifier 4 outputs the intensity R and phase θ that define the signal of the specific frequency extracted from the magnetic signal to the information processing device 9.

[0041] (Hardware configuration of information processing device) Fig. 6 is a diagram showing an example of a hardware configuration of an information processing device 9. As shown in Fig. 6, the information processing device 9 includes a processor 12, a RAM (Random Access Memory) 13, a reading unit 14, an internal storage unit 15, a display unit 16, an operation unit 17, and a communication interface 18.

[0042] The processor 12 is, for example, a CPU (Central Processing Unit) and executes arithmetic processing. The RAM 13 stores temporary information generated in association with the arithmetic processing of the processor 12. The processor 12 loads into the RAM 13 and executes the programs (including the detection program 10) stored in the internal storage unit 15.

[0043] The reading unit 14 reads information recorded on an optical recording medium 11 such as a CD-ROM (Compact Disk Read Only Memory).

[0044] The internal storage unit 15 is, for example, a hard disk drive, and stores various programs such as the detection program 10 and various data. Furthermore, the internal storage unit 15 stores phase information 20. The phase information 20 is generated by the execution of the detection program 10, and is used for the execution of the detection program 10.

[0045] The display unit 16 is, for example, a liquid crystal display, and displays a screen generated in response to the arithmetic processing of the processor 12. The operation unit 17 includes, for example, a keyboard, a mouse, etc., and accepts operation inputs by an operator.

[0046] The communication interface 18 communicates with an external device (for example, a server device 19) via a network. The server device 19 accumulates the results of processing by the information processing device 9, for example.

[0047] The detection program 10 includes a group of instructions for processing related to the detection of magnetic particles. The detection program 10 is recorded, for example, on an optical recording medium 11, read by a reading unit 14, and stored in an internal storage unit 15. Alternatively, the detection program 10 may be downloaded from a server device 19 via a communication interface 18 and stored in the internal storage unit 15.

[0048] (Flow of magnetic particle detection method) The method of detecting the magnetic particles 51, 52 in the detection system 100 includes a preparation phase and an actual measurement phase.

[0049] <Preparation phase> 7 is a flowchart showing an example of a process flow of the advance preparation phase. First, in steps S1 to S3, a first phase of a first signal of a specific frequency that is generated in response to a change in the magnetic moment of a magnetic particle 51, which is an example of a first magnetic particle, when an excitation magnetic field is applied is acquired.

[0050] Specifically, in step S1, the processor 12 of the information processing device 9 displays on the display unit 16 a screen that prompts the user to place the magnetic particles 51, which are an example of the first magnetic particles, in the measurement area 5. Upon receiving an input indicating that the placement of the magnetic particles 51 in the measurement area 5 has been completed, the processor 12 instructs the first power supply 7, the second power supply 8a, and the third power supply 8b to supply power. As a result, a zero magnetic field region 30 is formed in the measurement area 5, and an AC excitation magnetic field is applied. As a result, the magnetic sensor 3 measures a magnetic signal that indicates a change in the magnetic moment of the magnetic particles 51 present in the zero magnetic field region 30.

[0051] In step S2, the lock-in amplifier 4 extracts a first signal of a specific frequency that is generated in response to a change in the magnetic moment of the magnetic particle 51 from the magnetic signal measured in step S1, and identifies the intensity R1 and phase θ1 of the first signal. The phase θ1 is an example of the "first phase" in the present disclosure.

[0052] Fig. 8 is a diagram for explaining the process of step S2. As shown in Fig. 8, the intensity R1 and phase θ1 of the first signal are identified by expressing a point 91 having an X component X1 and a Y component Y1 output from the low-pass filters 43 and 44 of the lock-in amplifier 4 in polar coordinates.

[0053] Returning to FIG. 7, in step S3, the processor 12 acquires the intensity R1 and the phase θ1 of the first signal from the lock-in.

[0054] In the next steps S4 to S6, a second phase of a second signal of a specific frequency that is generated in response to a change in the magnetic moment of the magnetic particle 52, which is an example of the second magnetic particle, when an excitation magnetic field is applied is acquired.

[0055] Specifically, in step S4, the processor 12 of the information processing device 9 displays on the display unit 16 a screen that prompts the user to place the magnetic particles 52 in the measurement area 5. Upon receiving an input indicating that the placement of the magnetic particles 52 in the measurement area 5 has been completed, the processor 12 instructs the first power supply 7, the second power supply 8a, and the third power supply 8b to supply power. This forms a zero magnetic field region 30 in the measurement area 5, and applies an AC excitation magnetic field. As a result, the magnetic sensor 3 measures a magnetic signal that indicates a change in the magnetic moment of the magnetic particles 52 present in the zero magnetic field region 30.

[0056] In step S5, the lock-in amplifier 4 extracts a second signal of a specific frequency that is generated in response to a change in the magnetic moment of the magnetic particle 52 from the magnetic signal measured in step S4, and identifies the intensity R2 and phase θ2 of the second signal. The phase θ2 is an example of the "second phase" in the present disclosure.

[0057] Fig. 9 is a diagram for explaining the process of step S5. As shown in Fig. 9, the intensity R2 and phase θ2 of the second signal are identified by expressing a point 92 having an X component X2 and a Y component Y2 output from the low-pass filters 43 and 44 of the lock-in amplifier 4 in polar coordinates.

[0058] Returning to FIG. 7, in step S6, the processor 12 obtains the intensity R2 and the phase θ2 of the second signal from the lock-in up.

[0059] In step S7, the processor 12 calculates the phase difference Δθ (=θ1−θ2) between the phase θ1 and the phase θ2.

[0060] In step S8, the processor 12 calculates the rotation angle θ rot1 ,θ rot2 Determine the rotation angle θ rot1 is a rotation angle about the origin for moving the point 92 (see FIG. 8) on the X-axis or Y-axis. rot2 is a rotation angle about the origin for moving the point 91 (see FIG. 7) on the X-axis or Y-axis. rot1 ,θ rot2 is expressed by the following equations (7) and (8). θ rot1 =-θ2+(π / 2)×n (7) θ rot2 =-θ1+(π / 2)×n (8) n is an integer equal to or greater than 0. If n is an even number, the points 91 and 92 move onto the X-axis. If n is an odd number, the points 91 and 92 move onto the Y-axis.

[0061] In step S9, the processor 12 calculates the phase difference Δθ and the rotation angle θ rot1 ,θ rot2 and stores the phase information 20 in the internal storage unit 15.

[0062] <Measurement phase> The process flow of the measurement phase will be described with reference to Fig. 10 and Fig. 11. Fig. 10 is a flowchart showing an example of the process flow of the measurement phase. Fig. 11 is a diagram explaining the process of the measurement phase. In the measurement phase, magnetic particles 51, 52 are administered in advance into the test subject 6.

[0063] In step S11, the processor 12 of the information processing device 9 receives an input indicating that the placement of the test object 6 in the measurement area 5 has been completed, and instructs the first power supply 7, the second power supply 8a, and the third power supply 8b to supply power. This forms a zero magnetic field region 30 in the measurement area 5, and applies an AC excitation magnetic field. As a result, the magnetic sensor 3 measures a magnetic signal indicating a change in the magnetic moment of the zero magnetic field region 30 in the test object 6. Specifically, the magnetic sensor 3 measures a magnetic signal indicating a change in the magnetic moment of the magnetic particles 51, 52 present in the zero magnetic field region 30.

[0064] In step S12, the lock-in amplifier 4 detects a specific frequency ω generated in response to a change in the magnetic moment of the zero magnetic field region 30 from the magnetic signal measured in step S11. r The third signal is extracted at a specific frequency ω r , intensity R3 and phase θ3 are used, 2 / 1 R3cos(ω r The third signal is represented as (t+θ3) by the processor 12. The processor 12 acquires the third signal from the lock-in amplifier 4. Specifically, the processor 12 acquires the intensity R3 and phase θ3 that define the third signal.

[0065] As shown in FIG. 11, in polar coordinates, the coordinate (2 2 / 1Point 93 on the coordinate system R3, θ3) represents a third signal. The third signal is the sum of a first component resulting from a change in the magnetic moment of magnetic particle 51 and a second component resulting from a change in the magnetic moment of magnetic particle 52. That is, vector V3 starting from the origin and ending at point 93 is the sum of vector V1 corresponding to the first component and vector V2 corresponding to the second component. Vector V1 has a direction whose angle in polar coordinates has a phase θ1. Vector V2 has a direction whose angle in polar coordinates has a phase θ2.

[0066] Returning to Fig. 10, in step S13, the processor 12 selects a target particle from among the magnetic particles 51 and 52 in response to an input to the operation unit 17. In the following, the magnetic particles 51 and 52 that are not selected will be referred to as "other magnetic particles." In the example shown in Fig. 11, the processor 12 selects the magnetic particle 51 as the target particle.

[0067] Returning to Fig. 10, in steps S14 to S16, the processor 12 uses the phase θ1 and the phase θ2 to discriminate the components of the target particles (hereinafter referred to as "target components") among the magnetic particles 51 and 52 from the third signal. That is, when the magnetic particle 51 is selected as the target particle, the processor 12 specifies the magnitude of the vector V1 (see Fig. 11) corresponding to the first component. When the magnetic particle 52 is selected as the target particle, the processor 12 specifies the magnitude of the vector V2 (see Fig. 11) corresponding to the second component.

[0068] Specifically, in step S14, the processor 12 reads out the rotation angle corresponding to the target particle from the phase information 20 stored in the internal storage unit 15. When the magnetic particle 51 is selected as the target particle, the processor 12 reads out the rotation angle θ rot1 When the magnetic particle 52 is selected as the target particle, the processor 12 reads out the rotation angle θ rot2 The processor 12 performs a rotation process on the third signal by the rotation angle.

[0069] In the example shown in FIG. 11, since the magnetic particle 51 is selected as the target particle, the processor 12 sets the rotation angle θ rot1 The processor 12 reads out the rotation angle θ (=-θ2) of the point 93 representing the third signal with the origin as the center. rot1 Rotate only.

[0070] By performing the rotation process, the vectors corresponding to the components of the other magnetic particles are located on the X-axis or Y-axis. In the above formulas (7) and (8), if n is an even number, the vectors corresponding to the components of the other magnetic particles are located on the X-axis. In the above formulas (7) and (8), if n is an odd number, the vectors corresponding to the components of the other magnetic particles are located on the Y-axis. In the example shown in FIG. 11, n=0 and magnetic particle 51 is selected as the target particle, so vector V2 corresponding to magnetic particle 52 is located on the X-axis.

[0071] In the next step S15, the processor 12 calculates the intensity Ra of the component in the third signal whose phase is orthogonal to the phase of the other magnetic particles. That is, when the target particle is the magnetic particle 51, the processor 12 calculates the intensity Ra1 of the component in the third signal whose phase is orthogonal to the phase θ2. When the target particle is the magnetic particle 52, the processor 12 calculates the intensity Ra2 of the component in the third signal whose phase is orthogonal to the phase θ1.

[0072] 11, as described above, the vector V2 corresponding to the magnetic particle 52 is located on the X-axis. Therefore, the processor 12 determines the absolute value of the Y-coordinate of the point 93 after the rotation process as the intensity Ra1. Note that when the vector V2 corresponding to the magnetic particle 52 is located on the Y-axis, the processor 12 may determine the absolute value of the X-coordinate of the point 93 after the rotation process as the intensity Ra1.

[0073] In the next step S16, the processor 12 calculates the product Rb of the intensity Ra and 1 / sin(Δθ) as the target component of the target particle. That is, when the target particle is a magnetic particle 51, the processor 12 calculates the product Rb1 of the intensity Ra1 and 1 / sin(Δθ) as the target component. When the target particle is a magnetic particle 52, the processor 12 calculates the product Rb2 of the intensity Ra2 and 1 / sin(Δθ) as the target component.

[0074] 11, the product Rb1 of the intensity Ra1 and 1 / sin(Δθ) is calculated as the target component. The product Rb1 represents the magnitude of the vector V1.

[0075] In this way, the detection system 100 and the detection method according to the first embodiment can discriminate one component of two magnetic particles by using a phase difference based on the difference in relaxation time between the magnetic moments of the two magnetic particles.

[0076] When the zero magnetic field region 30 is scanned in the test subject 6, steps S11 to S16 are repeatedly executed while the zero magnetic field region 30 is being scanned. This allows the target component of the target particle to be calculated for each position and direction of the zero magnetic field region 30 in the test subject 6.

[0077] (Spatial Distribution Imaging) The processor 12 may execute a process (spatial distribution imaging) of generating an image showing a spatial distribution of magnetic particles present in the test object 6 based on the intensity R3 or the target component for each position and direction of the zero magnetic field region 30 in the test object 6. The processor 12 may execute the spatial distribution imaging using a known iterative image reconstruction method.

[0078] Fig. 12 is a flow chart showing an example of the flow of spatial distribution imaging. As shown in Fig. 12, in step S101, the processor 12 generates a sinogram (hereinafter referred to as a "measurement sinogram") from information indicating the intensity R3 or the target component for each position and direction of the zero magnetic field region 30. The sinogram is a signal map in which the horizontal axis indicates the scanning position of the zero magnetic field region 30 and the vertical axis indicates the angle φ (see Fig. 2) indicating the direction of the zero magnetic field region 30.

[0079] Next, in step S102, the processor 12 assumes a distribution of magnetic particles. In step S103, the processor 12 generates an assumed sinogram using the distribution assumed in step S102. In step S104, the processor 12 calculates the error between the measured sinogram generated in step S101 and the assumed sinogram generated in step S103. In step S105, the processor 12 determines whether the error is equal to or smaller than a predetermined convergence condition. If NO in step S105, the process returns to step S102.

[0080] The processor 12 repeats the processes from step S102 to step S104 until the error falls below the convergence condition.

[0081] If the result of step S105 is YES, in step S106, the processor 12 generates data (spatial distribution image data) showing an image showing the spatial distribution of magnetic particles corresponding to the hypothetical sinogram satisfying the convergence condition, and outputs the generated data. For example, the processor 12 causes the display unit 16 to display the image showing the spatial distribution of magnetic particles.

[0082] (Example of user interface screen) Fig. 13 is a diagram showing an example of a user interface screen provided by the detection system shown in Fig. 1. User interface screens 80, 81, and 82 shown in Fig. 13 are generated by the processor 12 and displayed on the display unit 16.

[0083] The user interface screen 80 includes an area 80a and buttons 80b and 80c. The area 80a displays a measurement sinogram generated from information indicating the position and strength R3 of the zero magnetic field region 30 for each direction.

[0084] The button 80b is a button for selecting the magnetic particles 51 as the target particles, and the button 80c is a button for selecting the magnetic particles 52 as the target particles.

[0085] When the button 80b is pressed, the processor 12 causes the display unit 16 to display a user interface screen 81. The user interface screen 81 includes areas 81a and 81b. Area 81a displays a measured sinogram generated from information indicating the target component (i.e., the product Rb1 corresponding to the magnetic particle 51, which is the target particle) for each position and direction of the zero magnetic field region 30. Area 81b displays a spatial distribution image corresponding to a hypothetical sinogram whose error with the measured sinogram displayed in area 81a is equal to or smaller than the convergence condition.

[0086] When the button 80c is pressed, the processor 12 causes the display unit 16 to display a user interface screen 82. The user interface screen 82 includes areas 82a and 82b. Area 82a displays a measured sinogram generated from information indicating the target component (i.e., the product Rb2 corresponding to the magnetic particle 52, which is the target particle) for each position and direction of the zero magnetic field region 30. Area 82b displays a spatial distribution image corresponding to a hypothetical sinogram whose error with the measured sinogram displayed in area 82a is equal to or smaller than the convergence condition.

[0087] By checking the user interface screen 81, the user can check the distribution of the magnetic particles 51 bound to the first protein in the test specimen 6. Furthermore, by checking the user interface screen 82, the user can check the distribution of the magnetic particles 52 bound to the second protein in the test specimen 6. In this way, according to the first embodiment, the user can simultaneously check the respective distributions of the two types of magnetic particles.

[0088] Embodiment 2 The detection system according to the second embodiment differs from the detection system 100 according to the first embodiment in that a frequency filter is provided instead of the lock-in amplifier 4. In the detection system according to the second embodiment, the frequency filter extracts a signal of a specific frequency from the magnetic signal output from the magnetic sensor 3, and outputs the extracted signal. The processor 12 of the information processing device 9 acquires the signal of the specific frequency that has passed through the frequency filter, and acquires the intensity and phase of the signal of the specific frequency.

[0089] Embodiment 3 The detection system according to the third embodiment differs from the detection system 100 according to the first embodiment in that it does not include the lock-in amplifier 4. In the detection system according to the third embodiment, the processor 12 of the information processing device 9 acquires a signal of a specific frequency by performing a fast Fourier transform on the magnetic signal received from the magnetic sensor 3 or a signal obtained by amplifying the magnetic signal. The processor 12 acquires the intensity and phase of the signal of the specific frequency.

[0090] Embodiment 4 The detection system according to the fourth embodiment has a phase difference Δθ and a rotation angle θ rot1 ,θ rot2 1. The difference is that instead of the phase information 20 indicating the phases θ1 and θ2, phase information indicating the phases θ1 and θ2 is generated and stored.

[0091] In the detection system according to the fourth embodiment, in the advance preparation phase, the processor 12 generates phase information indicating the phases θ1 and θ2, instead of steps S7 to S9 shown in FIG.

[0092] Furthermore, in the measurement phase, processor 12 performs the following process instead of steps S14 to S16 shown in Fig. 10. That is, when magnetic particle 51 is selected as the target particle, processor 12 performs a calculation according to the following formula (9), and when magnetic particle 52 is selected as the target particle, processor 12 performs a calculation according to the following formula (10). Note that in formulas (9) and (10), n is an integer equal to or greater than 0. When n is an even number, processor 12 acquires the real part of the calculation result as the target component, and when n is an odd number, processor 12 acquires the imaginary part of the calculation result as the target component.

[0093]

number

[0094] Embodiment 5. Fig. 14 is a diagram showing two types of magnetic particles detected by the detection system according to the fifth embodiment. As shown in Fig. 14, the detection system according to the fifth embodiment detects magnetic particles 53 and 54 instead of magnetic particles 51 and 52, as compared to the detection system 100 according to the first embodiment. The magnetic particle 53 is an example of a "first magnetic particle" in the present disclosure. The magnetic particle 54 is an example of a "second magnetic particle" in the present disclosure.

[0095] The magnetic particles 53 and 54 have different binding states with respect to the target substance 62 in the test object 6. That is, the magnetic particle 53 is not bound to the target substance 62. The magnetic particle 54 is bound to the target substance 62. When the magnetic particles 53 and 54 have a particle size in which Brownian motion is dominant, they have different Brownian relaxation times. Therefore, when an excitation magnetic field is applied, the phase of a signal of a specific frequency generated in response to a change in the magnetic moment of the magnetic particle 53 is different from the phase of a signal of a specific frequency generated in response to a change in the magnetic moment of the magnetic particle 54. Therefore, the detection system according to the fifth embodiment can discriminate the target particle component of the magnetic particles 53 and 54 from the signal of a specific frequency generated in response to a change in the magnetic moment of the zero magnetic field region including the magnetic particles 53 and 54 using the same method as the detection method according to the first embodiment.

[0096] The embodiments disclosed herein should be considered to be illustrative and not restrictive in all respects. The scope of the present disclosure is defined by the claims, not by the description of the embodiments described above, and is intended to include all modifications within the meaning and scope of the claims.

[0097] Various aspects of the present disclosure are summarized below as appendices. (Appendix 1) 1. A method for detecting magnetic particles using an alternating excitation magnetic field, comprising: acquiring a first phase of a first signal having a specific frequency generated in response to a change in the magnetic moment of the first magnetic particle when the excitation magnetic field is applied; acquiring a second phase of a second signal of a specific frequency generated in response to a change in the magnetic moment of the second magnetic particle when the excitation magnetic field is applied, wherein at the specific frequency, a relaxation time of the magnetic moment of the second magnetic particle is different from a relaxation time of the magnetic moment of the first magnetic particle, the detection method further comprising: acquiring a third signal of the specific frequency that is generated in response to a change in magnetic moment of a region of interest that includes the first magnetic particles and the second magnetic particles when the excitation magnetic field is applied; and discriminating a target component of a target particle from the third signal, the target particle being one of the first magnetic particles and the second magnetic particles, using the first phase and the second phase.

[0098] (Appendix 2) The target component is When the target particle is the first magnetic particle, the calculation is performed using an intensity of a component of the third signal having a phase orthogonal to the second phase, 2. The detection method of claim 1, wherein when the target particle is the second magnetic particle, the calculation is performed using the intensity of a component in the third signal that has a phase orthogonal to the first phase.

[0099] (Appendix 3) 3. The detection method of claim 2, wherein the target component represents the product of the intensity and 1 / sin(Δθ), where Δθ is the difference between the first phase and the second phase.

[0100] (Appendix 4) 4. The detection method according to any one of claims 1 to 3, wherein the first magnetic particles and the second magnetic particles have different particle sizes.

[0101] (Appendix 5) The detection method according to any one of appendix 1 to 3, wherein the first magnetic particles and the second magnetic particles have different binding states with respect to a target substance.

[0102] (Appendix 6) 6. The detection method of any one of claims 1 to 5, further comprising selecting the target particles from among the first magnetic particles and the second magnetic particles in response to an input.

[0103] (Appendix 7) scanning the area of ​​interest in an object under test that includes the first magnetic particles and the second magnetic particles; 7. The detection method according to any one of claims 1 to 6, further comprising generating an image showing a spatial distribution of the target particles in the specimen based on the target components.

[0104] (Appendix 8) 1. A detection system comprising: an excitation magnetic field applicator for applying an alternating excitation magnetic field to the target region; a magnetic sensor for detecting a magnetic signal indicative of a change in the magnetic moment of the region of interest; a processor; The processor, obtaining a first phase of a first signal of a specific frequency extracted from the magnetic signal when a first magnetic particle is placed in the target region; obtaining a second phase of a second signal at the particular frequency extracted from the magnetic signal when a second magnetic particle is disposed in the region of interest, where at the particular frequency a relaxation time of a magnetic moment of the second magnetic particle is different from a relaxation time of the magnetic moment of the first magnetic particle, and the processor further comprises: acquiring a third signal of the specific frequency extracted from the magnetic signal when an object to be inspected including the first magnetic particles and the second magnetic particles is placed in the target area; A detection system that uses the first phase and the second phase to discriminate a target component of a target particle from the third signal, the target particle being one of the first magnetic particles and the second magnetic particles.

[0105] (Appendix 9) The processor, When the target particle is the first magnetic particle, calculating the target component using an intensity of a component of the third signal having a phase orthogonal to the second phase; 9. The detection system of claim 8, wherein when the target particle is the second magnetic particle, the target component is calculated using the intensity of a component in the third signal that has a phase orthogonal to the first phase.

[0106] (Appendix 10) 10. The detection system of claim 9, wherein the component of interest represents the product of the intensity and 1 / sin(Δθ), where Δθ is the difference between the first phase and the second phase.

[0107] (Appendix 11) 11. The detection system of any one of claims 8 to 10, wherein the processor selects the target particles from among the first magnetic particles and the second magnetic particles in response to an input.

[0108] (Appendix 12) A detection system described in any of Appendix 8 to 11, wherein the processor generates an image showing the spatial distribution of the target particles in the test object based on the target components when the target area in the test object is scanned.

[0109] (Appendix 13) A program for causing a computer to execute a detection method for detecting magnetic particles using an alternating excitation magnetic field, The detection method includes: acquiring a first phase of a first signal having a specific frequency generated in response to a change in the magnetic moment of the first magnetic particle when the excitation magnetic field is applied; acquiring a second phase of the second signal at the specific frequency that is generated in response to a change in the magnetic moment of the second magnetic particle when the excitation magnetic field is applied, wherein at the specific frequency, a relaxation time of the magnetic moment of the second magnetic particle is different from a relaxation time of the magnetic moment of the first magnetic particle, the detection method further comprising: acquiring a third signal of the specific frequency that is generated in response to a change in magnetic moment of a region of interest that includes the first magnetic particles and the second magnetic particles when the excitation magnetic field is applied; and discriminating a target component of a target particle from the third signal, the target component being one of the first magnetic particles and the second magnetic particles, using the first phase and the second phase.

[0110] (Appendix 14) A computer-readable recording medium having the program described in appendix 13 recorded thereon. [Explanation of symbols]

[0111] 1 Excitation magnetic field applicator, 2 Zero magnetic field generator, 2a, 2b Electromagnet, 3 Magnetic sensor, 4 Lock-in amplifier, 5 Measurement area, 6 Test object, 7 First power source, 8a Second power source, 8b Third power source, 9 Information processing device, 10 Detection program, 11 Optical recording medium, 12 Processor, 13 RAM, 14 Reader, 15 Internal storage unit, 16 Display unit, 17 Operation unit, 18 Communication interface, 19 Server device, 20 Phase information, 30 Zero magnetic field region, 41, 42 Mixer, 43, 44 Low-pass filter, 45 Calculator, 51 to 54 Magnetic particles, 51a, 52a Probe, 60 Tissue, 62 Target material, 70, 72 Axis, 80, 81, 82 User interface screen, 80a, 81a, 81b, 82a, 82b Region, 80b, 80c Button, 100 detection system.

Claims

1. 1. A method for detecting magnetic particles using an alternating excitation magnetic field, comprising: acquiring a first phase of a first signal having a specific frequency generated in response to a change in the magnetic moment of a first magnetic particle when the excitation magnetic field is applied; acquiring a second phase of the second signal at the specific frequency that is generated in response to a change in the magnetic moment of the second magnetic particle when the excitation magnetic field is applied, wherein at the specific frequency, a relaxation time of the magnetic moment of the second magnetic particle is different from a relaxation time of the magnetic moment of the first magnetic particle, and the detection method further comprises: acquiring a third signal of the specific frequency that is generated in response to a change in a magnetic moment of a region of interest that includes the first magnetic particles and the second magnetic particles when the excitation magnetic field is applied; and discriminating a target component of a target particle from the third signal, the target particle being one of the first magnetic particles and the second magnetic particles, using the first phase and the second phase. The detection method, wherein discriminating the target component includes performing a rotation process on the third signal by a first rotation angle corresponding to the first phase when the target particle is the first magnetic particle, and performing a rotation process on the third signal by a second rotation angle corresponding to the second phase when the target particle is the second magnetic particle.

2. The target component is When the target particle is the first magnetic particle, the calculation is performed using an intensity of a component of the third signal having a phase orthogonal to the second phase, The detection method according to claim 1 , wherein when the target particle is the second magnetic particle, the calculation is performed using an intensity of a component of the third signal having a phase orthogonal to the first phase.

3. The method of claim 2 , wherein the component of interest represents a product of the intensity and 1 / sin(Δθ), where Δθ is a difference between the first phase and the second phase.

4. The detection method according to claim 1 , wherein the first magnetic particles and the second magnetic particles have different particle sizes.

5. The detection method according to claim 1 , wherein the first magnetic particles and the second magnetic particles have different binding states with respect to a target substance.

6. The detection method according to claim 1 , further comprising: selecting the target particles from among the first magnetic particles and the second magnetic particles in response to an input.

7. scanning the area of ​​interest in a specimen containing the first magnetic particles and the second magnetic particles; The detection method according to claim 1 , further comprising: generating an image showing a spatial distribution of the target particles in the specimen based on the target components.

8. A detection method described in any one of claims 1 to 3, wherein the first magnetic particle and the second magnetic particle bind to different proteins.

9. 1. A detection system comprising: an excitation magnetic field applicator for applying an alternating excitation magnetic field to the target region; a magnetic sensor for detecting a magnetic signal indicative of a change in the magnetic moment of the region of interest; a processor; The processor, obtaining a first phase of a first signal of a specific frequency extracted from the magnetic signal when first magnetic particles are placed in the target region; obtaining a second phase of a second signal at the particular frequency extracted from the magnetic signal when second magnetic particles are disposed in the region of interest, where at the particular frequency a relaxation time of a magnetic moment of the second magnetic particles is different from a relaxation time of the magnetic moment of the first magnetic particles, and the processor further comprises: acquiring a third signal of the specific frequency extracted from the magnetic signal when an object to be inspected including the first magnetic particles and the second magnetic particles is placed in the target area; discriminating a target component of a target particle from the third signal using the first phase and the second phase; A detection system, wherein discriminating the target component includes performing a rotation process on the third signal by a first rotation angle corresponding to the first phase if the target particle is the first magnetic particle, and performing a rotation process on the third signal by a second rotation angle corresponding to the second phase if the target particle is the second magnetic particle.

10. The processor, When the target particle is the first magnetic particle, calculating the target component using an intensity of a component of the third signal having a phase orthogonal to the second phase; The detection system of claim 9 , wherein when the target particle is the second magnetic particle, the target component is calculated using an intensity of a component in the third signal that has a phase orthogonal to the first phase.

11. 11. The detection system of claim 10, wherein the component of interest represents the product of the intensity and 1 / sin(.DELTA..theta.), where .DELTA..theta. is the difference between the first phase and the second phase.

12. The detection system of claim 9 , wherein the processor is operable to select the particles of interest from among the first magnetic particles and the second magnetic particles in response to an input.

13. The detection system of claim 9 , wherein the processor generates an image showing the spatial distribution of the target particles in the specimen based on the target components when the target area in the specimen is scanned.

14. A detection system described in any one of claims 9 to 11, wherein the first magnetic particle and the second magnetic particle bind to different proteins.

15. A program for causing a computer to execute a detection method for detecting magnetic particles using an alternating excitation magnetic field, The detection method includes: acquiring a first phase of a first signal having a specific frequency generated in response to a change in the magnetic moment of a first magnetic particle when the excitation magnetic field is applied; acquiring a second phase of the second signal at the specific frequency that is generated in response to a change in the magnetic moment of the second magnetic particle when the excitation magnetic field is applied, wherein at the specific frequency, a relaxation time of the magnetic moment of the second magnetic particle is different from a relaxation time of the magnetic moment of the first magnetic particle, and the detection method further comprises: acquiring a third signal of the specific frequency that is generated in response to a change in a magnetic moment of a region of interest that includes the first magnetic particles and the second magnetic particles when the excitation magnetic field is applied; and discriminating a target component of a target particle from the third signal, the target particle being one of the first magnetic particles and the second magnetic particles, using the first phase and the second phase. the discriminating between the target components includes, if the target particle is the first magnetic particle, performing a rotation process on the third signal by a first rotation angle corresponding to the first phase, and, if the target particle is the second magnetic particle, performing a rotation process on the third signal by a second rotation angle corresponding to the second phase.

16. The program described in claim 15, wherein the first magnetic particle and the second magnetic particle bind to different proteins.

17. A computer-readable recording medium having the program according to claim 16 recorded thereon.

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