KR102433170B1 - Magnetic particle spectroscopy - Google Patents

Abstract

One embodiment of the present invention provides a magnetic particle spectrometer. A magnetic particle spectrometer includes an excitation coil that generates a magnetic field that magnetizes magnetic particles; an inclinometer coil inserted into the excitation coil and including a receiving coil for receiving a particle signal from the magnetic particles, and a removal coil for canceling some of the signals generated from the receiving coil; a calibration coil positioned near the removal coil, a portion of which is inserted into the excitation coil and overlaps the excitation coil; and a position adjusting unit for adjusting the insertion depth of the calibration coil into the excitation coil to change the number of turns overlapping the excitation coil.

Description

Magnetic Particle Spectroscopy {MAGNETIC PARTICLE SPECTROSCOPY}

The present invention relates to a magnetic particle spectrometer, and more particularly, to a magnetic particle spectrometer having a fast and high sensitivity for imaging the concentration of magnetic nanoparticles (MNP).

Deep brain stimulation (DBS) of multiple areas of the brain is the most commonly used method to treat patients with neurological problems such as essential tremors such as Parkinson's disease and tremor. Recently, wireless magnetic thermal stimulation (WMS) has emerged as a new method of deep brain stimulation (DBS). It not only removes the limitations of other stimulation methods, but also offers the possibility of targeted stimulation without killing the cells around the stimulated site.

In WMS, magnetic nanoparticles (MNPs) target neurons and are exposed to low-frequency alternating magnetic fields, which are converted into heat by the MNPs to stimulate brain cells. However, since there is no monitoring system for brain activity, the effect of treatment cannot be accurately observed. Therefore, a brain activity monitoring system is needed to evaluate the process of WMS and increase its effectiveness.

The most widely used functional imaging techniques for monitoring the effects of brain stimulation are functional magnetic resonance imaging, positron emission tomography (PET), and electron copalography.

However, these techniques have limited safety due to low imaging precision, the need for radioactive elements, or limited measurement potential in brain surface regions.

Functional magnetic particle imaging (fMPI) detects changes in cerebral blood volume (CBV) by mapping magnetic particle concentrations using magnetic particle imaging (MPI). It is a promising modality for imaging.

Magnetic particle imaging (MPI) is a fast and sensitive technique for imaging of magnetic nanoparticles (MNP) concentrations. MPI directly measures and maps particle concentration at the measured spatial location. Functional MPI (fMPI) is a specific application of MPI that aims to detect changes in cerebral blood volume (CBV) via imaging.

Assuming that the concentrations of MNPs in CBV are uniform, the resulting concentrations of MNPs may indicate CBV changes. Magnetic particle spectroscopy (MPS) is essentially a zero-dimensional MPI scanner that can be used to perform spectroscopic studies and fMPI.

The brain functions in a non-implantable, non-invasive, radiation-free way. A variety of hardware developed for MPI can be used to monitor brain activity in fMPI, but fMPI needs to detect very small amounts of iron, so higher sensitivity is required. (26 ng iron for an 80 kg human, 53 ng iron for a 300 g rat).

Magnetic Particle Spectroscopy (MPS) is essentially a zero-dimensional MPI scanner or MPI scanner without a selection field to create a spatial encoding. Therefore, before developing a full fMPI, it is necessary to investigate whether MPS can achieve the necessary sensitivity for fMPI.

Since the sensitivity of magnetic particle spectroscopy (MPS) decreases in proportion to the square root of the coil radius, it is a great challenge to develop an MPS with a larger aperture size while ensuring the sensitivity required for fMPI.

An object of the present invention is to provide a magnetic particle spectrometer having a fast and high sensitivity for imaging the concentration of magnetic nanoparticles (MNP).

The technical problem to be achieved by the present invention is to provide an MPS for fMPI with a hole size of 50 mm that is compatible with the size of a mouse head.

The technical problems to be achieved by the present invention are not limited to the technical problems mentioned above, and other technical problems not mentioned can be clearly understood by those of ordinary skill in the art to which the present invention belongs from the description below. There will be.

In order to achieve the above technical object, an embodiment of the present invention provides a magnetic particle spectrometer. A magnetic particle spectrometer includes an excitation coil that generates a magnetic field that magnetizes magnetic particles; an inclinometer coil inserted into the excitation coil and including a receiving coil for receiving a particle signal from the magnetic particles, and a removal coil for canceling some of the signals generated from the receiving coil; a calibration coil positioned near the removal coil, a portion of which is inserted into the excitation coil and overlaps the excitation coil; and a position adjusting unit for adjusting the insertion depth of the calibration coil into the excitation coil to change the number of turns overlapping the excitation coil.

In an embodiment of the present invention, by correcting the residual induced voltage included in the output signal of the inclinometer coil when there are no magnetic particles inside the excitation coil by adjusting the position of the calibration coil by the position adjusting unit, can

In an embodiment of the present invention, the position of the receiving coil and the removal coil may be fixed with respect to the excitation coil.

In an embodiment of the present invention, the positioning unit includes a screw, the screw is screwed with the cylinder of the calibration coil and the cylinder of the excitation coil, and the insertion depth of the calibration coil is adjusted according to the rotation of the screw. can be adjusted.

In an embodiment of the present invention, the insertion depth of the calibration coil is adjusted, the number of turns of the coil crossover or magnetically coupled to the magnetic field generated in the excitation coil is changed, and thus the output signal can be adjusted.

In an embodiment of the present invention, the inclinometer coil may be a primary coil including the receiving coil and the removing coil having opposite winding directions.

In an embodiment of the present invention, the receiving coil and the removal coil are wound on the same cylinder, and the number of turns of the removal coil may be the same as the number of windings of the receiving coil.

In an embodiment of the present invention,

= 0으로 조정하기 위해 상기 교정 코일을 삽입함에 따라, L_receive와 R_receive는 증가하며, 상기 교정 코일의 삽입되는 권선수의 변경에 따라 (

L_receive) /R_receive 이 비선형적으로 변경될 수 있다.Phase correction is in the above equations

As the calibration coil is inserted to adjust to = 0, L_receive and R_receive increase, and according to the change in the number of inserted turns of the calibration coil (

L_receive) /R_receive may be changed non-linearly.

In an embodiment of the present invention, for amplitude calibration, using the number of calibration turns of the calibration coil determined through the phase correction, the amplitude of the receiving coil is changed as the calibration coil moves along the inside of the excitation coil, and the receiving coil and the receiving coil The removal coil may be fixed in position to maintain amplitudes A1 and A2.

In an embodiment of the present invention, the residual induced voltage in the gradient coil is as shown in Equation 1 below,

where Vrec, Vcali and Vcan are the voltage amplitudes of the receiving coil, the correction coil and the cancellation coil, respectively, and α is the phase difference between the total and cancellation signals of the receiving coil and the correction coil, to attenuate the residual induced voltage to zero, α phase is becomes -π, Vresidual becomes Vrec+Vcali-Vcan, and Vresidual is set to 0 by adjusting the amplitude of Vcali,

The α phase can be given as in Equation 2 above.

According to an embodiment of the present invention, it is possible to provide a magnetic particle spectrometer having a fast and high sensitivity for imaging the concentration of magnetic nanoparticles (MNP).

According to an embodiment of the present invention, it is possible to provide MPS for fMPI with a hole size of 50 mm compatible with the size of a rat head.

The MPS device of an embodiment of the present invention utilizes a 0.015T magnetic field at a frequency of 29.5 kHz and measures the small iron content of magnetic particles using an integrated method. Based on the integrated output signal, the MPS consists of an excitation coil, an inclinometer coil (receive coil and a rejection coil) and a calibration coil, capable of detecting up to 25 ng of Fe. Thus, the MPS of the examples of the present invention demonstrated that possible sensitivity to fMPI was achieved.

According to an embodiment of the present invention, a novel MPS for a rat head scale with an aperture size of 50 mm is presented. The new configuration of the Gradiometer coil with calibration coil and integrated measuring scheme can detect iron amounts up to 25 ng, making MPS designs feasible for fMPI requirements.

By adjusting the compensated phase and amplitude of the receiving coil with a calibration coil screw system, the induced signal in the excitation field can be significantly attenuated so that the output signal of the gradient measuring coil is in the input range of the analog-to-digital converter. ADCs for computer interfaces and integrated measurement methods can significantly remove noise from measurements.

It should be understood that the effects of the present invention are not limited to the above-described effects, and include all effects that can be inferred from the configuration of the invention described in the detailed description or claims of the present invention.

1 is a diagram illustrating the principle of measuring MNP concentration.
2 is a view showing a magnetic particle spectrometer according to an embodiment of the present invention.
3 is a view for explaining a vertical, planar, and asymmetrical arrangement as a general arrangement of the gradiometer coil.
4 is a view for explaining the order of the gradiometer coil.
5 is a graph for explaining the order of the gradiometer coil.
6 is a view for explaining the sensitivity of the receiving coil in relation to the diameter and length of the coil.
7 is a view for explaining an example of a gradiometer coil of a magnetic particle spectrometer according to an embodiment of the present invention based on the primary gradiometer coil.
8 shows an example of an electrical circuit of an MPS system.
9 is a diagram illustrating an example of hardware of the MPS.
10 is a view for explaining an operation when magnetic nanoparticles are put into a receiving coil.
11 is a graph for explaining the sensitivity of the coil.
12 is a view showing measurement results for explaining the sensitivity of the coil.
13 is a diagram illustrating an integrated measurement method of a device for explaining the sensitivity of a coil.
14 is a graph showing the results measured by the integrated measurement method.
15 is a diagram illustrating an output signal before and after calibration.
16 is a view showing the results of experiments on samples of different concentrations.

Since the present invention can have various changes and can have various forms, specific embodiments are illustrated in the drawings and described in detail in the text. However, this is not intended to limit the present invention to the specific disclosed form, it should be understood to include all modifications, equivalents and substitutes included in the spirit and scope of the present invention. In describing each figure, like reference numerals have been used for like elements.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Terms such as those defined in a commonly used dictionary should be interpreted as having a meaning consistent with the meaning in the context of the related art, and should not be interpreted in an ideal or excessively formal meaning unless explicitly defined in the present application. does not

Hereinafter, preferred embodiments of the present invention will be described in more detail with reference to the accompanying drawings.

The present invention discloses a fast and highly sensitive MPS. As an application, an embodiment of the present invention proposes an MPS-based design for developing an fMPI system to monitor brain activation. The most important task in fMPI implementation is to detect small amounts of iron content. The developed MPS system of this embodiment can detect the iron content of 25ng within 100 seconds. This shows that brain activation can be detected in the MPS system depending on the iron content.

1 is a diagram illustrating the principle of measuring MNP concentration.

1 shows a principle of measuring the concentration of MNP (magnetic nanoparticles) using a magnetic particle spectrometer (MPS). The analyzed electrical signal may indicate the concentration of MNP. For example, if a signal representing 53 ng iron could be detected by the MPS system, then functional magnetic particle imaging (fMPI) could detect brain activation in mice.

[MPS Design Concept]

MPI is a tracer-based imaging technique that uses the nonlinearity of the magnetic response of MNPs to detect the concentration of injected particles. Since the detection threshold of MNP is less limited by the background signal of the host tissue, MPI was expected to provide sensitivity enhancement compared to MRI. MPI can also measure the concentration of MNP more easily than MRI. For functional neuroimaging, we expect to use MPI to directly map CBV changes that occur in response to brain activation. Assuming that MNPs are uniformly distributed inside the human brain, they cannot cross the blood-brain barrier, particle concentration can reflect blood volume, and magnetic particle concentration can indicate CBV.

In the fMPI system designed for functional brain imaging in mice, MNPs can be injected at a concentration of about 10 mg Fe/kg (3 mg Fe for 300 g mice). The average rat blood is about 64 ml/kg. Given that each cortical brain voxel is 5% blood, a 3 mm isotropic cortical brain voxel contains 1.35 μl of blood. Thus, for a dose of 3 mg Fe, the voxel contains about 211 ng Fe. Activated regions of the brain were observed to have CBV changes of about 25%, indicating that the detection threshold of the detector should be less than 53 ng Fe in 300 g mice to detect neural activation.

When the MNP is in an MPS system, the uniform magnetic field H(t) of the excitation coil is used to magnetize the MNP. The time-varying magnetization M(t) of the particle is then induced in the excitation field. The particle's response is represented by the particle signal V(t). Since the magnetization behavior of particles is non-linear, the particle signal contains fundamental and higher harmonics of the excitation frequency. It is difficult to obtain a pure particle signal because the diamagnetic signal also contributes to the signal at the fundamental frequency. Therefore, it is desirable to use only harmonics to accurately identify the signal due to the MNP.

[Hardware design of MPS]

2 is a view showing a magnetic particle spectrometer according to an embodiment of the present invention.

The magnetic particle spectrometer of this embodiment includes an excitation coil, an inclinometer coil, a calibration coil and a positioning unit.

The inclinometer coil is inserted into the excitation coil, and may include a receiving coil and a removal coil for canceling a signal generated from the receiving coil.

A calibration coil is located adjacent to the removal coil, and a portion may be inserted into the excitation coil to overlap the excitation coil.

The positioning unit may adjust the insertion depth of the calibration coil into the excitation coil.

The signal received by the receiving coil includes the excitation signal along with the particle signal. Since the magnitude of the excitation signal is typically millions of times greater than the magnitude of the particle signal, the ADC cannot resolve both signals. Therefore, to bring the signal within the ADC range and improve the sensitivity of the MPS, an inclinometer coil method (adding a rejection coil) must be used to reject the excitation signal.

The magnetic particle spectrometer of this embodiment has a configuration for achieving high sensitivity of fMPI. That is, unlike the gradiometer coil used in the existing MPS, the magnetic particle spectrometer of this embodiment is provided with a receiving coil and a removal coil inside the excitation coil, and a part of the calibration coil is inserted into the excitation coil and overlapped (see FIG. 2). . The cancellation coil may remove the excitation signal included in the receiving coil. The aperture size of the MPS may vary depending on the target. For example, when targeting a rat brain, the aperture of the MPS may be chosen to be 50 mm so that the rat brain can fit inside.

<Gradiometer Coil Design>

Hereinafter, a principle of numerical design for improving sensitivity will be described with reference to FIGS. 3 to 7 .

3 is a view for explaining a vertical, planar, and asymmetrical arrangement as a general arrangement of the gradiometer coil.

The vertical type is generally selected because it has a large working space and easy maintenance design for adjustment. The horizontal type is a design that halves the cancellation work space and is difficult to adjust. In the asymmetric type, there is a difference in the number of turns between the sensing coil and the removal coil, so that the two coils have a difference in induction (that is, different phases).

4 is a view for explaining the order of the gradiometer coil.

The primary inclinometer rejects more than 99% of sources at 300b distance. Therefore, the sensitivity and SNR are the highest. The secondary inclinometer rejects more than 99% of sources at a distance of 30b, with reduced sensitivity and SNR compared to the primary inclinometer. The 3rd order inclinometer has lower sensitivity and SNR than the 2nd order inclinometer.

5 is a graph for explaining the order of the gradiometer coil.

Referring to FIG. 5 , the primary inclinometer is a preferable choice because the target of the inclinometer coil is sensitivity. However, in this case, other sources at a distance of less than 300b may contribute to the signal.

6 is a view for explaining the sensitivity of the receiving coil in relation to the diameter and length of the coil.

In conditions such as the diameter of the coil as shown in the upper figure of FIG. 6 , the gradiometer coil dimensions and coil radius can be designed in order to improve the sensitivity of the coil by referring to the following equations.

ρ is the effective coil sensitivity. P is the coil sensitivity at unit current. L is the coil inductance.

N is the number of turns. R is the coil radius. l is the coil length.

Referring to the above equation, the sensitivity decreases proportionally to √(^3). Therefore, it is desirable to minimize the radius according to the measurement target.

The lower graph of FIG. 6 is a graph for designing the gradiometer coil dimensions and coil length, and shows the optimal coil length l per radius R at different radii for the FOV center and FOV boundary.

Depending on the purpose of the coil sensor, measure at the center or near the boundary. The ratio can be selected from the center line or the border line. A common ratio is recommended if the FOV is at both the center and the border.

1.3≤/≤1.45 for radius > 40mm

7 is a view for explaining an example of a gradiometer coil of a magnetic particle spectrometer according to an embodiment of the present invention based on the primary gradiometer coil.

N _adjust << N _cancelation ; N _receive

The above condition means that the major order of the gradiometer coil is first order and the coil is slightly equal to second order to reduce other sources that are spaced apart.

N _calib + N _receive = N _cancelation (or Ncalib + Ncancellation = Nreceive)

가 된다.This condition covers the receive coil and the reject coil, so the phase difference

becomes

Phase correction:

Referring to the above formulas,

= 0으로 조정하기 위해 교정 코일은 교정 코일의 회전을 조정할 수 있고, L_receive와 R_receive는 증가할 것이며, 교정 코일의 권선수 변경 후에 (

L_receive) /R_receive 이 비선형적으로 변경될 수 있다.

= 0, the calibration coil can adjust the rotation of the calibration coil, L_receive and R_receive will increase, after changing the number of turns of the calibration coil (

L_receive) /R_receive may be changed non-linearly.

Amplitude Calibration:

- In practical applications, since the magnetic field inside the exciter coil is not uniform, the exact number of calibration turns of the coil can be defined through phase correction. Also, the receiving coil and the removing coil may be fixed in position to maintain amplitudes A1 and A2. As the calibration coil moves along the interior of the excitation coil, the amplitude of the receive coil may change.

3 to 7 above, in this embodiment, the model of the inclinometer coil may be selected as a primary coil including only a receiving coil and a removing coil having opposite winding directions for the highest sensitivity.

To obtain high sensitivity, the receiving coil or the removing coil can be designed according to the optimal relationship between the coil length l and the diameter D. For example, it may be (l(43) / D(50) = 0.866), which is exemplarily shown in FIG. 2 .

Once the coil aperture size is determined, this relationship can be used to calculate the coil length. If there is no MNP inside the excitation field, the output signal of the inclinometer coil should be 0. Accordingly, the number of turns of the removal coil may be selected to be equal to the number of turns of the receiving coil.

However, in real application conditions, there may be residual induced voltages in the output signal of the inclinometer coil. Therefore, in this embodiment, a calibration coil is added to correct the signal so that it is closest to zero. In this case, the displacements of the receiving coil and the removal coil are fixed relative to the excitation coil, and only the displacement of the calibration coil can be manipulated to adjust the output signal to zero. Accordingly, the number of turns of the coil crossover or magnetically coupled to the magnetic field generated in the excitation coil is changed, and thus the output signal can be adjusted.

For large bore size coils, the weight of all inclinometer coil components or the weight of the receiving coil or the removing coil is much greater than the weight of the calibration coil. Therefore, adjusting the position of the calibration coil is easier than moving another coil assembly inside the excitation coil. In this embodiment, the position adjusting unit is installed in the calibration coil to adjust the insertion depth of the calibration coil into the excitation coil. A screw may be employed as the positioning unit.

Using screws to move the calibration coil also makes the output signal adjustments as the receiving and removing coils are fixed in position, so only the adjusted signal from the calibration coil is changed while the signal from all other parts of the inclinometer coil is unaffected. Easier.

Also, since the calibrated signal of the calibration coil is much smaller than that of the other coils, the inclinometer coil output signal can be tuned more finely. Therefore, white Gaussian noise parasitic in the output signal can also be reduced. Thus, the sensitivity of the system is improved.

As described above, the inner diameter of the inclinometer coil may be selected according to a target, and may be selected as, for example, 50 mm. For example, a coil can be wound as a single layer on a 3D printed cylinder. For example, the outer diameter of the inclinometer coil is 60mm. 2 shows detailed dimensions of each coil used in the MPS by way of example. The receiving coil, removal coil and calibration coil rotate 75, 75 and 5 turns respectively. The diameter of the wire can be chosen as 80/46 AWG for receiving wideband frequency signals. In order to adjust the output signal to a null value, four plastic screws as a position adjuster pass through the flange portion of the calibration coil cylinder and can be screwed into the cylinder of the excitation coil. Thus, rotating the screw can advance and retract the position of the calibration coil with respect to the excitation coil.

<Excitation Coil Design>

2 to 7 , the outer diameter of the inclinometer coil and the inner diameter of the excitation coil are formed to be substantially the same, so that they can be securely assembled with minimal tolerance as shown in FIG. 2 . The excitation coil can be wound in two layers with 2 × 22 turns on two 3D printed cylinders. To produce a magnetic field amplitude of 0.015 T necessary to saturate the MNP, the diameter of the wire in the excitation coil can be chosen to be 5.4 mm to allow a current of up to 26 A.

Of course, these numerical specifications may vary depending on the measurement target, and the numerical ranges presented here are exemplary.

8 shows an example of an electrical circuit of an MPS system.

As an example of the circuit configuration of the magnetic particle spectrometer of this embodiment, the electric circuit shown in FIG. 3 may be adopted. The electrical circuit of the excitation coil is connected in series with a 0.5 μF capacitor to achieve the 29.5 kHz resonant circuit shown in FIG. 8 . Intended operating frequency. The excitation coil inductance is 58.2 μH and the ac resistance is 0.02 at 29.5 kHz. A function generator (KEYSIGHT 33500B series) generates an ac signal at a frequency of 29.5 kHz that is transmitted to a linear power amplifier (Model 7224 of AE Techron, Inc., Elkhart, Indiana, USA).

Since the output signal of the inclinometer coil is very small, the inclinometer coil is connected to a low noise preamplifier (model SR560) to improve the SNR of the system. It is then passed through a high-pass filter (model SR650) with a cutoff frequency of 80 kHz to obtain only the high-order harmonic particle signal.

After amplification and filtering, the signal from the nanoparticles is interfaced with PXI via NI DAQ (NI-6363 card-2 MS/s, 16b).

9 is a diagram illustrating an example of hardware of the MPS.

9 shows hardware for actually manufacturing the magnetic particle spectrometer of this embodiment. The interface hardware used in the experiments of MPS is shown, including the fabricated excitation coil and inclinometer coil.

[Calibration and measurement method]

A method of setting the residual induced voltage to zero by adjusting the position of the calibration coil by the position adjusting unit will be described.

10 is a view for explaining the operation of the MPS when the magnetic nanoparticles are put into the receiving coil.

Without the removal coil, the voltage measured at the receiving coil is the superposition of the particle signal U _P (t) induced by the time-varying magnetization and the excitation signal U _E (t) induced by the time-varying magnetic field.

The particle signal U _P (t) is significantly smaller than the induced excitation signal U _E (t). An analog-to-digital converter (ADC) cannot analyze the combined signal, so the excitation signal must be removed from the received signal before using the ADC.

- U_C(t)).The removal coil and the receiving coil have the same geometric parameters, but the coil polarity is different. The receiving coil and the removing coil are connected in series. The voltages measured at the cancellation coil U _C (t) and the excitation signal U _E (t) are equal in amplitude but opposite in direction (or U _E (t)

- U _C (t)).

The particle signal U _P (t) can be measured by combining the signals of the receiving coil and the removing coil as follows.

In practice, it is not easy to make the removal coil and the receiving coil the same. Therefore, in this embodiment, a calibration coil (calibration coil) is added to adjust accordingly. It is more convenient because only the position of the calibration coil needs to be controlled, and since the area movement of the calibration coil is smaller than that of the removal coil, the Ucalibration can be adjusted with high resolution.

11 is a graph for explaining the sensitivity of the coil.

g이다.Device measurements, radius = 2.5 cm. And / = 1.3 Sensitivity is best in the center. And when b = 2cm, the entire signal of the particle can be detected at a distance of 0.3b = 0.6cm to the receiving coil. If only the 3rd harmonic is detected, the iron measurand is 1

is g.

12 is a view showing measurement results for explaining the sensitivity of the coil.

12 shows a frequency range and a noise reception range of a received signal. Referring to FIG. 12 , a coil sensitivity of less than 100 ng can be detected using the 3rd, 5th, 7th, and 9th harmonics.

For example, in measurement MPI applications, the frequency range of the received signal for virus detection is 15 kHz to 40 kHz. The order of the signal can be used from 3rd to 9th order. Depending on the signal output of the filter, a second or higher order signal can be added. Since noise reception is white noise, there is no white noise range.

In the case of measurement MPI application, virus detection, the types of magnetic particles are as follows.

10 - 100 nm in diameter. Core size: 5 - 25 nm. Three magnetic particles can be selected.

diameter 45 - 65 nm; 5 - 6 nm core size (Resovist, Meito Sangyo Co. Ltd).

diameter 120 - 130 nm; 19nm core size (Perimag).

62 nm average diameter; 4.2nm core size (VivoTrax, Magnetic Insight)

13 is a diagram illustrating an integrated measurement method of a device for explaining the sensitivity of a coil.

Referring to FIG. 13 , the following relationship is established.

Usignal = Up + Unoise

Here, it is assumed that Unoise is white noise.

The integrated signal can be expressed by the following equation.

The signal of the particle is amplified with a gain of n times, and when n is sufficiently large, the noise can be expressed as the following equation.

Therefore, when the particle signal is smaller than the white noise, the particle signal can be detected in an integrated manner.

Because of the integration method, the limited frequency entering the signal can vary depending on the frequency sampling rate of the ADC. If the ADC's frequency sampling rate is less than the frequency harmonics obtained, the frame time will not be accurate and the integration may operate uncorrected.

As an example in this embodiment, the maximum frequency sampling rate of the device may be 2MSp/s. For example, the frequency of the ninth harmonic is 265.5 kHz.

14 is a graph showing the results measured by the integrated measurement method.

Radius = 2.5 cm and / = 1.3, and the sensitivity is best in the center.

And when b = 2cm, the entire signal of the particle can be detected at a distance of 0.3b = 0.6cm to the receiving coil. It detects the 3rd, 5th, 7th and 9th harmonics in an integrated way. As a result, the detected amount of iron is 25ng, and the result is checked by taking the result twice.

<Calibration>

Based on the method described with reference to FIGS. 10 to 14 , calibration may be performed.

Under experimental conditions, the magnetic field inside the excitation coil is not perfectly uniform. Therefore, in the absence of MNP, in the serial connection of the receiving coil and the removing coil, the output signal is quite high as the root mean square (rms) with a magnitude of 48mV. The residual voltage in the gradiometer coil (gradient coil) is as follows.

where Vrec, Vcali, and Vcan are the voltage amplitudes of the receiving coil, the correction coil, and the cancellation coil, respectively, and α is the phase difference between the total signal and the cancellation signal of the receiving coil and the correction coil. To attenuate the residual voltage to zero, the α phase needs to be -π. This is because Vresidual becomes Vrec+Vcali-Vcan, and Vresidual can be set to 0 by adjusting the amplitude of Vcali. The α phase is given by

The phase difference α may vary depending on the inductors (Lrec, Lcali, and Lcan) and resistors (Rrec, Rcali, and Rcan) of the receiving coil, the correction coil, and the removal coil, respectively.

15 is a diagram illustrating an output signal before and after calibration.

Using an LCR meter (B&K Precision Model 894) to measure the inductance and resistance of each coil, the phase difference α can be realized by adjusting the wire rotation of the calibration coil. The phase difference α is easier to adjust because of the small length and rotation of the calibration coil compared to the receiving coil and the removing coil. After calibration, the output signal of the inclinometer coil became significantly smaller at about 5 mV (see FIG. 15) with an attenuation of 44 dB, and it was confirmed that the white Gaussian noise was also significantly reduced.

<Measurement method>

Hereinafter, a method for measuring magnetic particles using the MPS of this embodiment will be described based on the method described in FIGS. 10 to 15 .

The MPS can be selected to detect the 4 odd harmonics from the 3rd to the 9th (265.5kHz) for the best performance of the ADC. If multiple harmonics participate in the output signal, significant white Gaussian noise can be added to the signal. In the magnetic particle concentration measurement using the magnetic particle spectrometer of this embodiment, the above-described integrated measurement method is used to reduce white Gaussian noise.

As shown in Equation 3 below, it is assumed that only the MNP signal u _p (t) and the white Gaussian noise signal u _noise (t) are included in the output signal u _signal (t) of the inclinometer coil measured in one frame (0.5 ms).

As shown in Equation 4 below, the integrated signal IntSig (t) becomes the sum of the output signals for n frames.

In the integrated signal, if n is large enough, the white Gaussian noise is zero or

으로 향할 정도로 시간이 충분히 길어진다. 따라서 IntSig (t)의 rms 값이 최종 출력이 된다. 이렇게 하면 처음에는 잡음의 진폭이 MNP 신호의 진폭보다 크더라도 통합 신호가 명확하게 표시된다.

time is long enough to go to Therefore, the rms value of IntSig(t) becomes the final output. This ensures that the integrated signal is clearly displayed even if the amplitude of the noise is initially greater than the amplitude of the MNP signal.

16 is a view showing the results of experiments on samples of different concentrations.

The actual experimental results are described as follows.

<A. Preparation of samples>

Meito Sangyo Company, Ltd. with a base concentration of 55 mg/ml. (Nagoya, Japan) Resovis particles were mixed with distilled water to make a test sample. Each sample has the same volume of 100 μl but the iron mass ranges from 25 ng to 10 μg, as can be seen in Fig. 16(a). A sample of distilled water without MNP is used as a control.

<B. Result>

To investigate the ability of fMPI to detect CBV, samples were placed one by one in MPS. The low-noise preamplifier was equipped with cut-off bandpass filters of 10 and 300 kHz with a gain of 5x and a high-pass filter of 80 kHz with a gain of 5x. The output signals obtained from the 10 μg, 5 μg, 500 ng, and 25 ng sample tests showed a clear difference between the particles with and without particles. Comparison results of the sample with 10 μg MNP and distilled water without MNP were obtained within 0.5 ms with direct signal measurement and within 0.5 s (n=1000) with the integrated method, which were obtained in Figs. 16(b) and (c) appears in These results show that the integrated method can maintain the accuracy of the measurement process.

The detection results of 5 μg, 500 ng, and 25 ng (RMS values of integrated 2000 frames, 10,000 frames, and 200,000 frames) are shown in FIGS. 16 (d) - (f). The lines in Fig. 16 (d) - (f) show the ability to detect MNP as the average value of the rms values of the integrated multiple frames. The signal from the 500 ng sample was also integrated over 0.5 s, but the signal was not different from that of distilled water. However, the 500 ng sample was successfully detected in 5 seconds (see Fig. 16(e)). Going down from 500 ng to 25 ng requires a 20-fold increase in sensitivity, so we need to increase the detection time threshold to 100 s. As shown in Fig. 16(f), the test was repeated twice with a 25ng sample to confirm the accuracy of the measurement.

As can be seen in Fig. 16(f), the 25 ng iron content can be detected by MPS using the integrated method. Therefore, this method could also be used to detect a target 53 ng iron content for rats. Since the MPS of this example can detect 25 ng/100 μl iron, a larger concentration of 53 ng/1.35 μl (blood volume of one voxel) can be detected by applying the selection field of MPI.

The above description of the present invention is for illustration, and those of ordinary skill in the art to which the present invention pertains can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. For example, each component described as a single type may be implemented in a dispersed form, and likewise components described as distributed may be implemented in a combined form.

The scope of the present invention is indicated by the following claims, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be construed as being included in the scope of the present invention.

D: Excitation coil diameter
R: Calibration coil diameter
b: distance between receiving coil and removing coil

Claims (10)

In a magnetic particle spectrometer,
an excitation coil that generates a magnetic field that magnetizes magnetic particles;
an inclinometer coil inserted into the excitation coil and including a receiving coil for receiving a particle signal from the magnetic particles, and a removal coil for canceling some of the signals generated from the receiving coil;
a calibration coil positioned near the removal coil, a portion of which is inserted into the excitation coil and overlaps the excitation coil; and
and a position adjusting unit for adjusting the insertion depth of the calibration coil into the excitation coil to change the number of turns overlapping the excitation coil.
It is characterized in that by correcting the residual induced voltage included in the output signal of the inclinometer coil when there are no magnetic particles inside the excitation coil by adjusting the position of the calibration coil by the position adjusting unit, it is close to zero,
The receiving coil inductance L is characterized in that it follows the following equation,

The phase correction of the inclinometer coil is

As the calibration coil is inserted to adjust to =0, L_receive and R_receive increase, and according to the change in the number of inserted windings of the calibration coil (

A magnetic particle spectrometer, characterized in that L_receive) /R_receive is changed non-linearly.
delete The method according to claim 1,
wherein the receiving coil and the removing coil are fixed in position with respect to the excitation coil.
The method according to claim 1,
The positioning unit includes a screw,
The screw is screwed with the cylinder of the calibration coil and the cylinder of the excitation coil, and the insertion depth of the calibration coil is adjusted according to the rotation of the screw.
The method according to claim 1,
The insertion depth of the calibration coil is adjusted, the number of turns of the coil crossover or magnetically coupled to the magnetic field generated in the excitation coil is changed, characterized in that the output signal is adjusted through this, magnetic particle spectrometer.
The method according to claim 1,
The inclinometer coil is a primary coil comprising the receiving coil and the removing coil having opposite winding directions, magnetic particle spectrometer.
7. The method of claim 6,
The receiving coil and the removing coil are wound on the same cylinder, and the number of turns of the removing coil is the same as the number of turns of the receiving coil.

delete The method according to claim 1,
For amplitude calibration, using the number of calibration turns of the calibration coil determined through the phase calibration, the amplitude of the receiving coil is changed as the calibration coil moves along the inside of the excitation coil, and the receiving coil and the canceling coil have amplitudes A1 and A2 A magnetic particle spectrometer, characterized in that it is fixed in a holding position.
The method according to claim 1,
Residual induced voltage in the inclinometer coil is as shown in Equation 1 below,

where Vrec, Vcali and Vcan are the voltage amplitudes of the receiving coil, the correction coil and the cancellation coil, respectively, and α is the phase difference between the total and cancellation signals of the receiving coil and the correction coil, to attenuate the residual induced voltage to zero, α phase is becomes -π, Vresidual becomes Vrec+Vcali-Vcan, and Vresidual is set to 0 by adjusting the amplitude of Vcali,

α phase is a magnetic particle spectrometer, characterized in that given as in Equation 2 above.

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