Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
  • A61B5/0515—Magnetic particle imaging
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/0017—Means for compensating offset magnetic fields or the magnetic flux to be measured; Means for generating calibration magnetic fields
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/12—Measuring magnetic properties of articles or specimens of solids or fluids
  • G01R33/1276—Measuring magnetic properties of articles or specimens of solids or fluids of magnetic particles, e.g. imaging of magnetic nanoparticles
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/24—Arrangements or instruments for measuring magnetic variables involving magnetic resonance for measuring direction or magnitude of magnetic fields or magnetic flux
  • G01R33/26—Arrangements or instruments for measuring magnetic variables involving magnetic resonance for measuring direction or magnitude of magnetic fields or magnetic flux using optical pumping
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
  • G01R33/32—Excitation or detection systems, e.g. using radio frequency signals
  • G01R33/323—Detection of MR without the use of RF or microwaves, e.g. force-detected MR, thermally detected MR, MR detection via electrical conductivity, optically detected MR

Definitions

• Magnetic nanoparticles inside the magnetic field - free region can be magnetized by a magnetic field other than the selection field, while magnetic nanoparticles outside the magnetic field - free region cannot react to an external magnetic field as they are magnetically saturated.
• another time - varying magnetic field also known as a dynamic magnetic field or a driving magnetic field, is applied.
• This dynamic magnetic field excites the magnetic nanoparticles in the magnetic field - free region, causing the magnetization of the magnetic nanoparticles to change dynamically.
• This time - varying magnetization is detected by a magnetic receiver. The detected magnetization originates from the magnetic nanoparticles that are present only in the magnetic field - free region and increases proportionally to the magnetic nanoparticle density.
• the dynamic field used in the magnetic particle imaging method and the time - varying magnetic field used in magnetic particle detection are generated by the transmitting electromagnetic coils.
• the response of magnetic particles to the variable magnetic field is usually measured by magnetic induction using receiving coils as described in the United States patent documents US2019223975 and US8183861 and European patent document EP3378389 in the known state of the art.
• the excitation of magnetic particles using transmitting coils and the reception of signals from the receiving coils are performed simultaneously. Therefore, not only the magnetization of magnetic particles but also the magnetic field generated by the transmitting coil induces voltage in the receiving coils. Since the voltage induced by the transmitting coil is much higher than the voltage induced by the magnetic particle magnetization, it is necessary to separate the magnetic particle magnetization from the effect of the transmitting magnetic field. In the known state of the art, filtering, gradiometric receiving coils and conjugate receiving system methods are used for this purpose.
• the filtering method takes advantage of the fact that the magnetization signal of magnetic nanoparticles is non-linear and contains high harmonic frequency components.
• the first harmonic of the magnetic particle - induced signal is at the same frequency as the transmitting coil signal.
• the signal induced in the receiving coil is passed through a band - stop filter to suppress the first harmonic of the received signal as much as possible.
• This eliminates the transmitting coil signal (Bente, Klaas, et al. "Electronic field free line rotation and relaxation deconvolution in magnetic particle imaging.” IEEE Transactions on Medical Imaging 34.2 (2014): 644 - 651).
• this method eliminates the signal of the transmitting coil while also eliminating the magnetization signal of the magnetic particles, a large portion of the magnetic particle signal is lost, reducing the signal - to - noise ratio.
• reverse polarity compensation coils are used, which are arranged outside the transmitting coils and generate a magnetic field in the opposite direction with respect to the transmitting coil in the region where the particles are located. Therefore, much more current is supplied to the transmitting coil to apply the desired magnetic field to the magnetic particles compared to the case without compensation coils. This both reduces system efficiency and increases system cost and power consumption as higher current generators have to be used. Since said compensation coils reduce the magnetic field outside of the imaging field, the atomic magnetometer has to be placed far away from the imaging field. Since the magnetic field decreases with the cube of the distance, such a distant placement of the atomic magnetometer results in a significant decrease in the received signal level and signal - to - noise ratio.
• the purpose of the present invention is to provide a high - precision magnetic field measurement device that can efficiently measure the magnetization response of magnetic particles in a sensing region, especially at excitation frequencies higher than 5 kHz, but also at low excitation frequencies such as 0-5 kHz.
• the magnetization response of magnetic nanoparticles is detected by magnetic field sensors based on optically detected magnetic resonance (ODMR) measurement.
• ODMR optically detected magnetic resonance
• This type of sensor is able to measure the magnetization directly and not the derivative of the magnetic flux as in inductive sensing. This eliminates the limitations of in the known state of for low - frequency excitation and large magnetic particle diameter. Furthermore, the development of ODMR sensors, which have higher sensitivity than inductive coils, can improve the sensitivity of magnetic particle detection and imaging.
• nitrogen - vacancy defect centers which are naturally found in diamonds or synthetically obtainable, are preferably used.
• the negatively charged boron - vacancy defect center in the hexagonal boron nitrate structure or the single carbon defect center or the double - vacancy defect center in the silicon carbide structure can be used.
• the magnetic field - free region generated by the transmitting coil elements can be linear, so that optically sensed magnetic resonance sensors can be positioned in a linear array. In this way, the sensor coverage areas and signal - to - noise ratio can be increased. It is also possible to apply Ramsey, Pulsed ODMR or Spin echo ODMR methods using pulsed signals in the known state of the art to increase measurement sensitivity.
• the magnetization signal due to the relaxation response of the magnetic particles after the excitation of the transmitting coils is terminated is measured by the ODMR method. In this case, since the magnetic field sensor is not affected by the magnetic field emitted by the transmitting coil element before relaxation, the response can be measured precisely.
• the negatively charged nitrogen - vacancy defect centers in diamond can be four - directional due to the structure of the atomic bonds.
• a single negatively charged nitrogen defect center can be used for magnetic field measurement, or a diamond with many negatively charged nitrogen defect centers can be also used.
• the direction of the magnetic field generated by the magnetic nanoparticles is determined by the direction of the magnetic field generated by the transmitting coil.
• the angle of the diamond containing a single or plurality of negatively charged nitrogen - vacancy defect centers is adjusted to maximally detect the signal in the magnetic particle magnetization direction.
• the vectorial variation of magnetic particle magnetization is measured by following the resonance frequencies of negatively charged nitrogen defect centers in four different directions in the ODMR spectrum.
• Magnetic particles react to the magnetic field by two different mechanisms, Neel and Brownian: In the Neel mechanism, the particles do not physically rotate and the magnetization changes rapidly, while in the Brownian mechanism, the particles physically rotate. By measuring the vector magnetic field, it is possible to distinguish between these two mechanisms.
• the magnetization change mechanics of the particles can be obtained and information about the ambient viscosity and temperature can be obtained.
• Figure 1- A representative schematic view of an embodiment of the inventive magnetic field measuring device.
• Figure 2- A simplified representative view of the magnetic field distribution generated by the transmitting coils in one embodiment of the inventive magnetic field measuring device.
• Figure 3- A representative view of a diamond crystal containing a negatively charged nitrogen - vacancy defect center in its structure in one embodiment of the inventive magnetic field measurement device.
• Figure 4- A representative view of the optical excitation and optical emission in the energy diagram of negatively charged nitrogen - vacancy defect centers in diamond in one embodiment of the inventive magnetic field measuring device.
• Figure 5- A representative view of the optical excitation and optical emission of the energy diagram of negatively charged nitrogen - vacancy defect centers in diamond in a microwave - excited state in one embodiment of the inventive magnetic field measuring device.
• Figure 6a- A drawing representing the magnetic field around the line where the magnetic field generated by the transmitting coils is zero in an embodiment of the inventive magnetic field measuring device.
• Figure 6b- A drawing representing a representative representation of an embodiment of the inventive magnetic field measuring device, wherein the position of the line at which the magnetic field generated by the transmitting coils is zero is changed by the magnetic field generated by the compensation coils.
• Figure 6c- A drawing representing a representative representation of the first magnetic field generated by the transmitting coils, the magnetic field generated by the compensation coils and the total magnetic field around the line where the magnetic field generated by the transmitting coils is zero in an embodiment of the inventive magnetic field measuring device.
• Figure 7- A representative schematic view showing the placement of the compensation coils in an embodiment of the inventive magnetic field measuring device.
• Figure 8- A representative schematic view showing the placement of the compensation coils in another embodiment of the inventive magnetic field measuring device.
• the energy state of the optically excited negatively charged nitrogen - vacancy defect centers (DC) changes to the excited state ( 3 E), but when the optical excitation is stopped, the already excited negatively charged nitrogen - vacancy defect centers (DC) return to their unexcited state, i.e. their base energy states ( 3 A). During this return, the negatively charged nitrogen - vacancy defect centers (DC) emit photons at the optical frequency ( Figure 4).

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• Physics & Mathematics (AREA)
• Health & Medical Sciences (AREA)
• Condensed Matter Physics & Semiconductors (AREA)
• General Physics & Mathematics (AREA)
• Life Sciences & Earth Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Engineering & Computer Science (AREA)
• Biophysics (AREA)
• Medical Informatics (AREA)
• Nanotechnology (AREA)
• Chemical & Material Sciences (AREA)
• Pathology (AREA)
• Biomedical Technology (AREA)
• Heart & Thoracic Surgery (AREA)
• Radiology & Medical Imaging (AREA)
• Molecular Biology (AREA)
• Surgery (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Investigating Or Analyzing Materials By The Use Of Magnetic Means (AREA)

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• 2023
  • 2023-11-28 EP EP23837815.2A patent/EP4577105A1/de active Pending

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