CN111208461A - Device and method for measuring concentration and distribution of boron-containing medicine in human brain - Google Patents
Device and method for measuring concentration and distribution of boron-containing medicine in human brain Download PDFInfo
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Abstract
The invention relates to a device and a method for measuring the concentration and distribution of boron-containing medicaments in human brain. The device mainly comprises a main magnetic field coil, a gradient coil, a radio frequency coil and a control and data processing system, wherein the main magnetic field coil is wound by adopting a superconducting wire, and the control and data processing system comprises a computer for controlling each part and processing data, a spectrometer, a transceiving converter and a plurality of power amplifiers under the control of the computer. The method comprises the steps of detecting the de-excitation signals of hydrogen atoms and boron atoms by utilizing a nuclear magnetic resonance detection principle to obtain corresponding spatial distribution image data, calibrating the boron atom de-excitation signals by using a standard boron compound die body with known concentration, registering and fusing the boron atom spatial distribution image data and human anatomy image data to obtain quantitative image data of the boron atom concentration in the human anatomy image so as to provide relevant basic data for formulating BNCT treatment plans or other applications.
Description
Technical Field
The invention relates to a device and a method for measuring the concentration and distribution of boron-containing medicaments in human brain, which can be used for obtaining boron (B) before boron neutron capture radiotherapy (BCNT) treatment10B) The distribution and concentration information of the medicament in the body provides relevant basic data for the formulation of a Treatment Plan (TPS), and can also be used for monitoring the distribution and concentration information of the boron-containing medicament for other purposes.
Background
BNCT can perform accurate treatment on tumors on the order of microns, so the distribution and concentration of boron-loaded drugs in the treatment target area must be determined before treatment and compared with the expected distribution of a treatment plan to achieve efficient treatment of tumors and protect normal tissues. If quantitative distribution information of boron drugs is not obtained before BNCT treatment, the uncertainty of treatment dosage can be caused, the treatment effect is influenced, and unnecessary damage is brought to normal tissues.
The current methods for obtaining boron-containing drug distribution and concentration information are mainly based on two methods besides the method based on the measurement of the boron-containing drug concentration in blood: firstly, radioactive labeling is carried out on boron-containing drugs, radioactive devices (such as SPECT, PET and the like) are adopted for radioactive ray measurement, and the distribution of radioactivity represents the distribution of the boron-containing drugs; and secondly, carrying out magnetic resonance sensitive element marking on the boron-containing medicine, measuring by adopting magnetic resonance and the like, and representing the distribution of the boron-containing medicine by using the intensity distribution of magnetic resonance signals.
Among these, the method based on the measurement of the concentration of boron-containing drugs in blood has two disadvantages: firstly, the measurement time is long, and the measured boron-containing drug concentration cannot represent the boron-containing drug concentration during treatment; secondly, the concentration of the lesion area is estimated on the assumption that the blood ratio of the tumor is a constant value, but in practice, the blood ratio of the tumor varies with the individual patient, with the type/position of the tumor, with the position within the tumor, and with time, and a method assuming a fixed value is too extensive. Such conventional methods have therefore begun to be gradually replaced by new methods.
The methods based on radiolabelling boron-containing drugs suffer from several problems: (1) availability of radiolabeled boron-containing drugs; (2) certainty of the proportion of radiolabeled boron-containing drug within the total boron-containing drug; (3) the cost of the medicine is increased; (4) the additional dose of radiopharmaceutical given to the patient; (5) the spatial resolution of nuclear medicine methods is low; (6) are not approved by drug administration.
The method for marking boron-containing drugs based on MRI sensitive elements has the following problems: (1) MRI sensitive elements mark the availability of boron-containing drugs; (2) increasing the cost of the drug.
The practical application and the application effect of the methods are substantially hindered by the problems.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a novel device and a novel method for measuring the concentration and distribution of boron-containing drugs in human brain, so as to obtain more accurate measurement data in real time and facilitate practical application.
The technical scheme of the invention is as follows:
apparatus for measuring the concentration and distribution of boron-containing drugs in the brain of a human, comprising:
the device comprises a main magnetic field coil, a magnetic field sensor and a magnetic field sensor, wherein the main magnetic field coil is used for forming a uniform and stable main magnetic field in a measurement area, is arranged in a hollow cylindrical low-temperature container and is wound;
the gradient coil is used for forming a three-dimensional gradient magnetic field in the measuring area and is arranged on the inner side of the main magnetic field coil;
a radio frequency coil for transmitting and receiving radio frequency electromagnetic waves to and from the measurement region, which may be generally disposed inside the gradient coil or at other suitable locations, the frequencies of the radio frequency electromagnetic waves including boron nuclear magnetic resonance excitation frequencies and hydrogen nuclear magnetic resonance excitation frequencies;
a control and data processing system for controlling the operation of the gradient coil and the radio frequency coil according to the nuclear magnetic resonance detection principle, according to the received boron atoms10B) The de-excitation signal emitted in the de-excitation process is used for calibrating the de-excitation signal of the boron atom by using a standard boron compound die body with known concentration, the spatial distribution image data of the boron atom is obtained by calculation, and (C) according to the received hydrogen atom1H) And (3) calculating the spatial distribution image data of the hydrogen atoms by a de-excitation signal sent in the de-excitation process, determining the human anatomy image data according to the spatial distribution image data of the hydrogen atoms, and carrying out image registration and fusion on the spatial distribution image data of the boron atoms and the human anatomy image data to obtain the quantitative image data of the boron atom concentration in the human anatomy image.
The superconducting wire for winding the main magnetic field coil is preferably a magnesium diboride superconducting wire.
The gradient coils and the radio frequency coil are preferably axially centered on the main magnetic field coil.
The measurement region may be a bore of a magnetic field housing, the magnetic field housing being cylindrical, the main magnetic field coil, the cryogenic vessel, the gradient magnetic field coil and the radio frequency coil being mounted within the magnetic field housing.
The radio frequency coil is a hydrogen boron binuclear element radio frequency coil, and the working frequency is the resonance frequency of hydrogen atoms and boron atoms.
The standard boron compound die body with known concentration can be arranged in the measuring area and can be in a small ball shape or other shapes, the device for installing the standard boron compound die body can be arranged, the small ball is positioned in the measuring area through the support, and the standard boron compound die body and the detected human body are detected together. The support can be fixed on any fixing piece at any position, for example, a magnetic field shell, and can also be worn on the head of the detected person (made into a shape capable of being worn on the head). In the detection process, a de-excitation signal of a standard boron compound die body is obtained, and then the boron concentration under each part (voxel) in a human body is calibrated according to the relation between the concentration and the intensity of the de-excitation signal.
The head of the person to be detected can move into or out of the middle of the hole cavity of the magnetic field shell along with the movement of the examination bed.
The control and data processing system may include:
the spectrometer is used for generating and outputting frequency or waveform control signals of the gradient coil and the radio frequency coil under the control of a computer, controlling working parameters of the gradient coil related to the condition of the gradient magnetic field, further controlling the condition of the gradient magnetic field, controlling the working frequency of the radio frequency coil, further controlling the frequency of radio frequency electromagnetic waves transmitted or received by the radio frequency coil, wherein the control signal output of the gradient coil is amplified by a gradient power amplifier and then is connected to a corresponding control end of the gradient coil, and the control signal output of the radio frequency coil is amplified by a radio frequency power amplifier and then is connected to a corresponding control end of the radio frequency coil;
the gradient power amplifier is used for amplifying the power of a gradient coil control signal sent by the spectrometer;
the radio frequency power amplifier is used for amplifying the power of the radio frequency control signal sent by the spectrometer;
the receiving and transmitting converter is used for generating and outputting a control signal of the working mode of the radio frequency coil under the control of a computer, controlling the working mode of the radio frequency coil, and controlling the control signal output to be accessed to a corresponding control end of the radio frequency coil;
and the computer is used for controlling the work of the spectrometer and the transceiving converter, the control signal output ends for controlling the work of the spectrometer and the transceiving converter are respectively connected to the corresponding control ends of the spectrometer and the transceiving converter, receiving a deactivation signal containing space positioning information from the radio frequency coil and carrying out corresponding calculation processing to form quantitative image data of the boron atom concentration in the human anatomy image, and the transceiving conversion control signal transmission and the deactivation signal transmission between the computer and the radio frequency coil can share the same cable or link, and can also be respectively provided with respective cables or links.
A method for measuring the concentration and distribution of boron-containing medicine in human brain by using the Nuclear Magnetic Resonance (NMR) detection principle and selectively exciting the hydrogen atoms in brain by electromagnetic waves with specific frequency under the control of gradient magnetic field in a constant main magnetic field1H) Or a boron atom (10B) Positioning a de-excitation signal emitted by excited atoms in the de-excitation process by using a gradient magnetic field, respectively calculating to obtain spatial distribution image data of hydrogen atoms and boron atoms according to the obtained de-excitation signal, forming high-resolution human anatomy image data according to the spatial distribution image data of the hydrogen atoms, calibrating the received de-excitation signal of the boron atoms by using a standard boron compound die body with known concentration, and carrying out image registration and fusion on the spatial distribution image data of the boron atoms and the human anatomy image data to obtain quantitative image data of the boron atom concentration in the human anatomy image.
The magnets for generating the main magnetic field are preferably superconducting coils which can be arranged in a hollow-cylindrical cryogenic vessel, wound with superconducting wire, which is provided with a refrigerator system.
The superconducting wire for winding the main magnetic field coil is preferably a magnesium diboride superconducting wire.
The electromagnetic waves used to selectively excite the hydrogen and boron atoms of the brain may be generated by a radio frequency coil operating at a frequency in the range of the resonance frequencies of the hydrogen and boron atoms, for example, 6MHz to 64MHz, capable of transmitting and receiving radio frequency electromagnetic waves in this range under the control of a spectrometer.
The radio frequency coil can be used for receiving the de-excitation signals of the hydrogen atoms and the boron atoms, and the transmitting and receiving working modes of the radio frequency coil are switched through the transceiving converter.
The invention has the beneficial effects that: the signals emitted by boron and hydrogen atoms in the process of excitation withdrawal are positioned and detected by adopting the magnetic resonance principle, the radioactive marking of boron-containing drugs is not needed, the damage to a human body caused by introducing radioactive substances is avoided, meanwhile, MRI sensitive elements are not needed to be introduced for marking, the obstacle caused by the availability of the radioactive boron-containing drugs and the MRI sensitive elements for marking the boron-containing drugs for practical application in the reality is thoroughly eliminated, the high drug cost caused by marking is avoided, the real-time measurement can be carried out, and in the background of the prior art, the high-precision measurement result can be obtained; the distribution image of boron and the distribution image of hydrogen can be obtained in the same measurement, and the boron image and the hydrogen image with high resolution ratio are registered and fused to form the accurately positioned boron distribution image in the human body.
The invention is suitable for any boron-containing medicament, can reflect the real and real-time distribution of the boron-containing medicament, has no additional radiation dose, and can carry out dose supervision and verification.
Drawings
FIG. 1 is a schematic diagram of an equipment system used in the present invention.
Detailed Description
As shown in fig. 1, the present invention is based on the nuclear magnetic resonance detection principle to detect, detect or measure, the hardware architecture mainly includes a main magnetic field coil 2 forming a main magnetic field, a gradient coil 4 forming a gradient magnetic field, a radio frequency coil 3 transmitting and receiving radio frequency electromagnetic waves, and a control and data processing system 10 for controlling and processing each part of the system, the main magnetic field coil is wound by a superconducting wire 1, wherein the control and data processing system includes a computer for controlling and processing each part and data, a spectrometer and a transceiver converter under the control of the computer, the spectrometer control signal output of the computer is connected to the corresponding control terminal of the spectrometer, the transceiver switching signal output of the radio frequency coil is connected to the corresponding control terminal of the transceiver converter, the gradient coil control signal output of the spectrometer is connected to the corresponding control terminal of the gradient coil after being amplified by a gradient power amplifier, the control signal output of the radio frequency coil of the spectrometer is amplified by a radio frequency power amplifier and then is connected to the corresponding control end of the radio frequency coil, and the de-excitation signal received by the radio frequency coil enters the corresponding input end of the computer. Therefore, the computer can control the work of the whole system under the support of corresponding software, and carry out corresponding data processing, finally form quantitative image data of boron atom concentration under the human anatomy image, and the data can be displayed as a corresponding image on a display and can be used as corresponding basic data for making a BNCT treatment plan. The conversion of the boron concentration and the boron-containing drug concentration can be performed according to specific boron-containing drug components.
The control and data processing system may be of any suitable prior art, wherein the control part and the data processing part may be of separate devices, such as a control system of an existing MRI apparatus and a computer for data processing, or may be integrated together, with or without a common part, or even the same device may be used for all functions of control and data processing.
The main magnetic field coil is wound by a superconducting wire 1 and is arranged in a low-temperature container, low temperature required by superconductivity is formed according to the prior art, the gradient coil can be a conventional coil or a superconducting coil, and when the superconducting coil is adopted, the gradient coil also needs to be arranged in the low-temperature container.
During detection, a person to be detected lies on the examination bed 5, and the head enters the middle of the hole for detection.
The invention can directly obtain the boron-containing medicine distribution in vitro, non-invasively and in real time before and during BNCT treatment, can obtain the quantitative distribution image of boron atoms in a human body, is suitable for all boron-containing medicines and does not need radioactive labeling.
The boron detected by the invention is particularly boron-10 (B)10B) The purpose of hydrogen excitation is to obtain a high-resolution human anatomy image, and the image resolution of boron-10 atom distribution is low and needs to be fused with a hydrogen atom high-resolution image for use.
Electromagnetic waves with specific frequency are used for selectively exciting hydrogen and boron atoms in the brain, and a gradient magnetic field is used for positioning signals emitted by the excited atoms in the de-excitation process, so that a distribution image of the hydrogen and boron atoms is obtained. And (3) calibrating the received signal by using a standard boron compound die body with the concentration to obtain a quantitative image of the boron atom concentration.
Magnetic resonance imaging uses the frequency of the electromagnetic wave in relation to the main magnetic field used, and when the magnetic induction is B (in Tesla), the frequency of the electromagnetic wave used to excite hydrogen is 42.58MHz xb, and the frequency of the electromagnetic wave used to excite boron-10 is 4.58MHz xb. For example:
example 1: main magnetic field strength is 1.5 Tesla, excited hydrogen: (1H) The frequency of the electromagnetic wave is 42.58MHz x 1.5=63.87 MHz, exciting boron-10: (10B) The frequency of the electromagnetic wave used was 4.58MHz x 1.5=6.87 MHz.
Example 2: the main magnetic field strength was 3 Tesla, the frequency of the electromagnetic wave used to excite hydrogen was 42.58MHz x 3=127.74 MHz, and the frequency of the electromagnetic wave used to excite boron-10 was 4.58MHz x 3= 13.74 MHz.
The device of the invention can adopt the following technical means:
1) with magnesium diboride (MgB)2) The wire was wound as a main magnetic field coil, the coil diameter being 40 cm.
2) The main magnetic field coil is placed in a hollow barrel type low-temperature container, and the low-temperature container is cooled to 20K by a refrigerator. Under the temperature condition, the resistance of the magnesium diboride wire is zero.
3) A strong current is passed through a main magnetic field coil in a superconducting state, and a magnetic field of 1.5 tesla is generated inside the coil.
4) The gradient magnetic field coil and the radio frequency coil are arranged in the axial middle of the low-temperature container.
5) The radio frequency coil can transmit and receive radio frequency electromagnetic waves of 6MHz-64MHz under the control of a spectrometer or a computer.
6) During the examination, the head of the tested person is positioned in the magnetic field generated by the magnesium diboride coil.
7) According to the requirement, under the coordination of the gradient magnetic field, the radio frequency electromagnetic waves with different frequencies can be used for exciting boron or hydrogen atoms at different positions of the human brain, and the required frequency can be selected according to the strength of the main magnetic field.
8) Boron or hydrogen atoms are demagnetized and then emit electromagnetic waves, the electromagnetic waves are matched with a gradient magnetic field, a radio frequency receiving coil receives signals, and spatial position information is obtained through the gradient magnetic field.
9) The quantitative image of boron can be obtained through mathematical processing and can be registered and fused with the high-resolution image of hydrogen.
The bed may be of any suitable known technique, for example, any suitable bed for magnetic resonance examination, in which the front end of the bed (the flat or planar-like portion without a support on which a person may lie) is capable of extending into the bore with the head in the middle of the bore for examination. However, the existing examining table is often simpler and single in function, is often only suitable for the supine posture, but is difficult to adapt to the patient who cannot keep the head still for a long time.
As an improvement, the front part of the bed body is provided with a left vertical guard plate and a right vertical guard plate, and the plane of the guard plates is perpendicular to the left and right direction so as to be capable of blocking and protecting two sides of the head. The protective plates are connected with the lathe bed in a sliding mode through transverse guide rails or rails, transverse rotating screws are arranged below the lathe bed, the left side and the right side of each rotating screw are installed on the lathe bed through bearings and preferably located below the lathe bed, transverse long holes located above the rotating screws are formed in the lathe bed, driving connecting ends are arranged at the lower ends of the protective plates and penetrate through the transverse long holes in the lathe bed, nuts in threaded fit with the rotating screws are fixedly connected to the lower ends of the driving connecting ends, the spiral directions of the left threads and the right threads of the rotating screws are opposite, and therefore the left protective plates and the right protective plates can be driven to synchronously transversely move in opposite directions or move back to back through rotation of the rotating screws, so that the contact distance or pressure between the left protective plates and the head can be synchronously adjusted.
The guide rail or the track for realizing the sliding connection between the guard plate and the bed body can be arranged on the bottom surface of the bed body and aligned with the transverse long hole, and a structure matched with the guide rail or the track is arranged on the driving connecting end so as to realize the sliding between the guard plate and the bed body. The sliding connection based on rails or tracks described above may be achieved using a slide rail mechanism that is commercially available or other suitable prior art.
The transverse long hole can be a whole piece or a left and a right pieces and respectively corresponds to the left and the right guard plates, and the span of the transverse long hole is adapted to the possible moving range of the guard plates in actual use. When the shield is not needed, the shield can be moved away from the head.
The medial surface of backplate (the right flank of left backplate, the left surface of right backplate) is equipped with flexible or elastic bed course, the medial surface shape of bed course should adopt ergonomic design, has better laminating with the head, avoids bringing the damage for the patient because of the extrusion.
The hardware part without the control and data processing system and the examination bed (the parts of the above technical solutions except the control and data processing system and the examination bed) can be used as a technical solution or a product, and the product can perform corresponding work under the control of the corresponding control and data processing system. The hardware part (excluding the control and data processing system) without the control and data processing system and with the examination table can also be used as a technical scheme or a product, which can carry the examined person and carry out corresponding work under the control of the corresponding control and data processing system.
The device for measuring the concentration and the distribution of the boron-containing medicament in the brain can be used for implementing any method for measuring the concentration and the distribution of the boron-containing medicament in the brain, or adopting any method for measuring the concentration and the distribution of the boron-containing medicament in the brain to carry out measurement.
The technical means disclosed by the invention can be combined arbitrarily to form a plurality of different technical schemes except for special description and the further limitation that one technical means is another technical means.
Claims (10)
1. The device for measuring the concentration and distribution of boron-containing drugs in the brain of a human is characterized by comprising:
the device comprises a main magnetic field coil, a magnetic field sensor and a magnetic field sensor, wherein the main magnetic field coil is used for forming a uniform and stable main magnetic field in a measurement area, is arranged in a hollow cylindrical low-temperature container and is wound;
the gradient coil is used for forming a three-dimensional gradient magnetic field in the measuring area and is arranged on the inner side of the main magnetic field coil;
the radio frequency coil is used for transmitting radio frequency electromagnetic waves to the measuring region and receiving the radio frequency electromagnetic waves from the measuring region, and the frequency of the radio frequency electromagnetic waves comprises a boron atom nuclear magnetic resonance excitation frequency and a hydrogen atom nuclear magnetic resonance excitation frequency;
the control and data processing system is used for controlling the work of the gradient coil and the radio frequency coil according to a nuclear magnetic resonance detection principle, calibrating the de-excitation signal of the boron atom by using a standard boron compound die body with known concentration according to the de-excitation signal sent by the received boron atom in the de-excitation process, calculating the spatial distribution image data of the boron atom, calculating the spatial distribution image data of the hydrogen atom according to the de-excitation signal sent by the received hydrogen atom in the de-excitation process, determining the human anatomy image data according to the spatial distribution image data of the hydrogen atom, and carrying out image registration fusion on the spatial distribution image data of the boron atom and the human anatomy image data to obtain the quantitative image data of the boron atom concentration in the human anatomy image.
2. The apparatus of claim 1 wherein the superconducting wire used to wind the main magnetic field coil is a magnesium diboride superconducting wire.
3. The apparatus of claim 1 wherein said gradient coil and said radio frequency coil are axially centered on a main magnetic field coil.
4. The apparatus of claim 1 wherein said measurement region is within a bore of a magnetic field housing, said magnetic field housing being cylindrical, said main magnetic field coil, cryogenic vessel, gradient magnetic field coil and radio frequency coil being mounted within said magnetic field housing.
5. The apparatus according to any of claims 1-4, wherein said control and data processing system comprises:
the spectrometer is used for generating and outputting frequency or waveform control signals of the gradient coil and the radio frequency coil under the control of a computer, controlling working parameters of the gradient coil related to the condition of the gradient magnetic field, further controlling the condition of the gradient magnetic field, controlling the working frequency of the radio frequency coil, further controlling the frequency of radio frequency electromagnetic waves transmitted or received by the radio frequency coil, wherein the control signal output of the gradient coil is amplified by a gradient power amplifier and then is connected to a corresponding control end of the gradient coil, and the control signal output of the radio frequency coil is amplified by a radio frequency power amplifier and then is connected to a corresponding control end of the radio frequency coil;
the gradient power amplifier is used for amplifying the power of a gradient coil control signal sent by the spectrometer;
the radio frequency power amplifier is used for amplifying the power of the radio frequency control signal sent by the spectrometer;
the receiving and transmitting converter is used for generating and outputting a control signal of the working mode of the radio frequency coil under the control of a computer, controlling the working mode of the radio frequency coil, and controlling the control signal output to be accessed to a corresponding control end of the radio frequency coil;
and the computer is used for controlling the work of the spectrometer and the transceiving converter, and a control signal output end for controlling the work of the spectrometer and the transceiving converter is respectively connected to corresponding control ends of the control spectrometer and the transceiving converter, receives a de-excitation signal which is originated from the radio frequency coil and contains space positioning information, performs corresponding calculation processing, and forms quantitative image data of boron atom concentration under the human anatomy image.
6. A method for measuring the concentration and distribution of boron-containing medicine in human brain includes such steps as selectively exciting hydrogen atoms or boron atoms in brain by electromagnetic waves with specific frequency under the control of gradient magnetic field in constant main magnetic field, locating the exciting signal generated by excited atoms in exciting process by gradient magnetic field, calculating the spatial distribution image data of hydrogen atoms and boron atoms according to the obtained exciting signal, generating high-resolution anatomical image data of human body, scaling the exciting signal of boron atoms by standard boron compound die body with known concentration, and fusing the spatial distribution image data of boron atoms with the anatomical image data of human body to obtain the quantitative image data of boron atom concentration in anatomical image.
7. The method according to claim 6, characterized in that the magnets for generating the main magnetic field are superconducting coils arranged in a hollow cylindrical cryogenic vessel wound with superconducting wire, the cryogenic vessel being provided with a refrigerator system.
8. The method of claim 7 wherein the superconducting wire used to wind the main magnetic field coil is a magnesium diboride superconducting wire.
9. The method according to any one of claims 6 to 8, wherein the electromagnetic waves for selectively exciting hydrogen and boron atoms in the brain are generated by a radio frequency coil operating at the resonance frequency of hydrogen and boron atoms, capable of transmitting and receiving radio frequency electromagnetic waves in this range under the control of a spectrometer.
10. The method of claim 9, wherein said rf coil is adapted to receive de-excitation signals of hydrogen atoms and boron atoms, and wherein said rf coil is switched between transmit and receive modes of operation by a transmit-receive converter.
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