A quantitative evaluation method for in vivo molecular probes based on xenon / phosphorus multi-nuclear magnetic resonance

Abstract

The present invention discloses a quantitative evaluation method of in vivo molecular probes based on xenon / phosphorus multi-nuclear magnetic resonance, which obtains the corresponding curve between the pH value of the molecular probe saturated solution and the molecular probe saturation concentration and 129 Sensitivity distribution diagram of the Xe transceiver integrated coil; obtain the hydrogen proton magnetic resonance structure image of the test area of ​​the test object; obtain the 3D 31 P chemical shift imaging data, to obtain molecular probe 129 Xe magnetic resonance signal distribution image; obtain pH value distribution image of the detection object to be tested area; obtain molecular probe concentration distribution image in the detection object to be tested area; calculate the molecular probe position coordinates of the detection object to be tested area and the molecular probe concentration distribution image; calculate the molecular probe position coordinates of the detection object to be tested area and the molecular probe concentration distribution image; calculate the molecular probe position coordinates of the detection object to be tested area and the molecular probe concentration distribution image; calculate the molecular probe concentration distribution image ... 129 The present invention can realize the concentration of molecular probes and the molecular probes that are difficult to detect in vivo without damage. 129 Quantitative measurement of parameters such as Xe apparent binding rate.

Description

Technical Field

[0001] The present invention relates to the field of magnetic resonance technology, and in particular to a quantitative evaluation method for in vivo molecular probes based on xenon / phosphorus multi-nuclear magnetic resonance, which is suitable for quantitatively evaluating parameters such as the concentration and apparent binding rate of magnetic resonance molecular probes in vivo based on multi-nuclear magnetic resonance technology. Background Art

[0002] Molecular Magnetic Resonance Imaging (MRI) technology can measure and characterize biological tissues and organs at the molecular level. Clinical MRI instruments mainly 1 H imaging, the realization of molecular MRI is generally achieved by changing the relaxation time of tissues through paramagnetic contrast agents, thereby changing the image contrast [Mulder WJM, et al., NMR in Biomedicine, 2006, 19, 142–164]. 1 Molecular magnetic resonance imaging of H is affected by background signals from other tissues and organs in the image, making it more difficult to identify regions of interest.

[0003] Multinuclear molecular magnetic resonance imaging (MRI) technology based on hyperpolarized xenon molecular probes has great prospects in detecting microscopic biological processes. 1H has a very high magnetic resonance signal sensitivity and lacks in vivo background signal interference. Although xenon itself is nonspecific, its excellent chemical shift sensitivity allows it to exhibit a new magnetic resonance chemical shift after reversible binding to caged molecules (molecular probes), enabling detection and imaging of the distribution of molecular probes in vivo. However, due to the complex factors affecting the xenon signal within molecular probes in vivo, current multinuclear molecular MRI methods based on hyperpolarized xenon can only simply image the distribution of molecular probes in vivo and cannot obtain quantitative information about the multinuclear molecular probes, such as their in vivo concentration and binding rate with xenon. The in vivo concentration of molecular probes is a key indicator for evaluating the in vivo application of multinuclear molecular probes, as this parameter directly influences the estimation of their detection limit. Furthermore, unlike in vitro imaging of multinuclear molecular probes in solution, the in vivo environment is more complex. The volume of multinuclear molecular probes delivered to the brain is lost due to the long delivery route, and the spaces that would otherwise be available for xenon binding are occupied by other small biomolecules. Therefore, the apparent binding rate of multinuclear molecular probes with xenon in vivo is also a key factor influencing the xenon signal intensity of multinuclear molecular probes in vivo experiments. Quantitative measurement of multinuclear molecular probe concentration and apparent binding rate can reflect the in vivo properties of the designed probes, thereby better guiding the structural design of multinuclear molecular probes and improvements in experimental methods. Currently, published literature and patents do not provide information on the measurement of these two indicators. Summary of the Invention

[0004] The purpose of the present invention is to address the above-mentioned problems existing in the prior art and to provide a quantitative evaluation method for in vivo molecular probes based on xenon / phosphorus multi-nuclear magnetic resonance.

[0005] The above-mentioned purpose of the present invention is achieved by the following technical means:

[0006] The quantitative evaluation method of an in vivo molecular probe based on xenon / phosphorus multi-nuclear magnetic resonance includes the following steps:

[0007] Step 1: Obtain the corresponding curve between the pH value of the molecular probe saturated solution and the molecular probe saturation concentration , get 129 Sensitivity distribution diagram S1 of the Xe transceiver integrated coil;

[0008] Step 2: Obtain a hydrogen proton magnetic resonance structural image of the target area ;

[0009] Step 3: Get the 3D image of the area to be tested 31 P chemical shift imaging data , obtain molecular probes 129 Xe magnetic resonance signal distribution image ;

[0010] Step 4. Based on 3D 31 P chemical shift imaging data Generate pH distribution image of the test area of ​​the test object ;

[0011] Step 5: Proton magnetic resonance imaging of the target area based on the target area Confirm the position coordinates of the molecular probe in the area to be tested , based on molecular probes 129 Xe magnetic resonance signal distribution image and pH distribution image of the test area of ​​the test object Generate a molecular probe concentration distribution image in the target area ;

[0012] Step 6: Based on the sensitivity distribution map S1, the molecular probe 129 Xe magnetic resonance signal distribution image Perform signal correction and calculate the position coordinates of the molecular probe in the detection area of ​​the detection object Molecular probes at 129 Apparent binding rate of Xe .

[0013] The corresponding curve between the pH value of the molecular probe saturated solution and the molecular probe saturation concentration in step 1 is generated based on the following steps:

[0014] Obtain a series of pH values ​​of molecular probe saturated solutions with different pH values ​​and the corresponding molecular probe saturation concentrations, and draw the corresponding curve between the pH value of the molecular probe saturated solution and the molecular probe saturation concentration .

[0015] As mentioned in step 1 129 The sensitivity distribution diagram S1 of the Xe transceiver coil is generated based on the following steps:

[0016] Get a uniform 129 Xe gas phantom package 129 Xe transceiver surface coil 129 Xe gas imaging 129 Sensitivity distribution diagram S1 of the Xe transceiver integrated surface coil.

[0017] As described above, the molecular probe in step 3 129 Xe magnetic resonance signal distribution image Generated based on the following steps:

[0018] Step 3.1: Get the 3D image of the area to be tested 31 P chemical shift imaging data Sp;

[0019] Step 3.2: Collect the molecular probes in the test area of ​​the test object, the first calibration tube and the second calibration tube. 129 Molecular probes obtained by 3D UTE sequence scanning with Xe 129 Xe magnetic resonance signal distribution image .

[0020] The pH distribution image of the test area of ​​the test object in step 4 above Generated based on the following steps:

[0021] The 3D obtained from step 3 31 Chemical shift imaging data p The chemical shift distribution map of inorganic phosphate was obtained by pixel-by-pixel peak fitting. , and then calculate pixel by pixel according to the following formula to obtain the pH distribution image of the test area of ​​the detection object , pH distribution image of the test subject's brain area The pH value of the kth pixel is the chemical shift distribution map of inorganic phosphate (Pi) The pH value corresponding to the k-th pixel,

[0022] ;

[0023] in, Chemical shift distribution of inorganic phosphate The value of the kth pixel, Chemical shift distribution of inorganic phosphate The pH value corresponding to the k-th pixel.

[0024] The molecular probe concentration distribution image in the test area in step 5 above Obtained based on the following steps:

[0025] Step 5.1: The molecular probe obtained in step 3 129 Xe MRI signal distribution The pH distribution image of the test area of ​​the test object obtained in step 4 is superimposed The pH value of the molecular probe distribution in the test area of ​​the test object is obtained, and then the hydrogen proton magnetic resonance structure image of the test area of ​​the test object obtained in step 2 is obtained. Confirmed molecular probe position coordinates in the area to be tested , get the position of the molecular probe in the detection area of ​​the detection object pH value at ;

[0026] Step 5.2: The corresponding curve between the pH value of the molecular probe saturated solution and the molecular probe saturation concentration obtained in step 1 is obtained. The position of the molecular probe in the target area is obtained in step 5.1. pH value at , calculate pixel by pixel to obtain the position of the molecular probe in the area to be tested Concentration distribution at ,

[0027] ;

[0028] in, is the concentration of the molecular probe saturated solution at pH 7.4, The position of the molecular probe in the area to be tested The pH value at for The corresponding molecular probe saturation concentration.

[0029] As mentioned above, the sensitivity distribution diagram S1 of the molecular probe in step 6 is 129 Xe magnetic resonance signal distribution image Signal calibration is performed based on the following steps:

[0030] Based on the results obtained in step 1 129 Sensitivity distribution diagram of Xe transceiver surface coil S1 for the molecular probe obtained in step 3 129 Xe magnetic resonance signal distribution image Perform signal correction to obtain the corrected molecular probe 129 Xe magnetic resonance signal distribution image I C The average signal value of the first calibration tube area , the average signal value of the second calibration tube area and the position coordinates of the molecular probe in the detection area of ​​the detection object Signal distribution at , the correction formula is as follows:

[0031] ;

[0032] in, For the calibrated molecular probe 129 Xe magnetic resonance signal distribution image The value of the j-th voxel, Molecular probes 129 Xe magnetic resonance signal distribution image The value of the j-th voxel, for 129 Sensitivity distribution of the Xe transceiver surface coil The value of the j-th voxel;

[0033] The position coordinates of the molecular probe in the detection area of ​​the object to be detected in step 6 Molecular probes at 129 Apparent binding rate of Xe Obtained based on the following steps:

[0034] The position coordinates of the molecular probe in the detection area of ​​the detection object Molecular probes at 129 Apparent binding rate of Xe The calculation is based on the following formula:

[0035] ;

[0036] in, The molecular probe position of the detection object is The pixel volume, is the volume of the molecular probe solution in the first calibration tube and the second calibration tube, is the concentration of the molecular probe saturated solution in the first calibration tube, is the concentration of the molecular probe saturated solution in the second calibration tube.

[0037] A computer device includes a memory and a processor, wherein the memory stores a computer program and the processor implements each step of the above-mentioned quantitative evaluation method based on xenon / phosphorus multi-nuclear magnetic resonance in vivo molecular probe when executing the computer program.

[0038] A computer-readable storage medium stores a computer program, which, when executed by a processor, implements the steps of the quantitative evaluation method based on xenon / phosphorus multi-nuclear magnetic resonance in vivo molecular probe.

[0039] A computer program product includes a computer program, which implements the steps of the above-mentioned quantitative evaluation method based on xenon / phosphorus multi-nuclear magnetic resonance in vivo molecular probe when executed by a processor.

[0040] Compared with the prior art, the present invention has the following beneficial effects:

[0041] 1. Establish the corresponding relationship between the saturation concentration of the molecular probe saturated solution and the pH value of the molecular probe saturated solution through in vitro calibration, as well as the in vivo 31 The pH distribution obtained by P magnetic resonance spectroscopy imaging is used to obtain the concentration distribution of molecular probes;

[0042] 2. Correct the multi-nuclear signal in the molecular probe in vivo by measuring the coil sensitivity distribution to achieve accurate quantification of the multi-nuclear molecular probe signal in vivo;

[0043] 3. By simultaneously testing the first calibration tube and the second calibration tube 129 Xe signal and the body of the object to be measured 129 The Xe signal is measured to obtain the molecular probe and 129 Apparent binding rate distribution of Xe. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 is a flow chart of the present invention;

[0045] Figure 2 It is a corresponding curve diagram between the pH value of the saturated solution of A and the saturated concentration of A;

[0046] Figure 3 yes 129 Schematic diagram of the sensitivity distribution of the Xe transceiver surface coil;

[0047] Figure 4 It is a schematic diagram of the acquisition state of the acquisition object. Among them, (a) is the acquisition time 31 P transceiver birdcage coil, first calibration tube, second calibration tube, magnetic resonance examination bed, 129 Schematic diagram of the Xe transceiver surface coil and the detection object; (b) is a ventilation diagram;

[0048] Figure 5 It is the concentration distribution image of A in the brain area of ​​the test subject;

[0049] Figure 6 It is a Chinese hole A and 129 Xe apparent binding rate distribution image;

[0050] In the picture: 101— 31 P transceiver birdcage coil; 102 - first calibration tube; 103 - second calibration tube; 104 - magnetic resonance examination bed; 105 - 129 Xe transceiver integrated surface coil; 106 - detection object. DETAILED DESCRIPTION

[0051] In order to facilitate those skilled in the art to understand and implement the present invention, the present invention is further described in detail below in conjunction with embodiments. It should be understood that the embodiments described herein are only used to illustrate and explain the present invention and are not used to limit the present invention.

[0052] Example 1:

[0053] In this embodiment, the in vivo molecular probe is the hyperpolarized xenon molecular probe cryptophane-A (doi: 10.1038 / ncomms1151), hereinafter referred to as "cryptophane-A", and the region to be tested is the target region of interest of the living subject, and in this embodiment, the region to be tested is specifically the brain region.

[0054] In this embodiment, the collection of data related to the detection object is based on the following conditions:

[0055] like Figure 4 (a) and Figure 4 As shown in (b), 31 The P transceiver birdcage coil 101 is located in the center of the MRI. The subject 106 wears a breathing mask and lies on the MRI bed 104. Then the pH value is 7.4, the saturation concentration is C0, and the volume is V A The saturated solution of Acupuncture Point A was injected into the body of the test subject through atomization, inhalation, etc., and the final pH value of the saturated solution of Acupuncture Point A with a saturated concentration of C0 was delivered to the brain area; the test subject 106 wore 129 The Xe transceiver integrated surface coil 105, the first calibration tube 102 and the second calibration tube 103 are respectively placed 129 Outside the Xe transceiver integrated surface coil 105, the first calibration tube 102 is filled with a saturated solution of Xe A with a set concentration of C1 and a volume of Vml, and the second calibration tube 103 is filled with a saturated solution of Xe A with a set concentration of C2 and a volume of Vml. The breathing mask of the test subject 106, the first calibration tube 102 and the second calibration tube 103 are all 129 After the Xe gas transmission system is connected, the saturated solution of Acupoint A is delivered to the brain area. 129 The Xe gas transmission system continuously supplies hyperpolarized Xe to the test object, the first calibration tube 102 and the second calibration tube 103. 129 The mixture of Xe gas and oxygen makes the brain tissue of the test object and the first calibration tube 102 and the second calibration tube 103 129 The Xe concentration reaches saturation. The MRI bed 104 is placed in the MRI machine so that the head of the subject 106 is positioned at 31 P is the center of the transceiver birdcage coil 101.

[0056] like Figure 1 As shown, the quantitative evaluation method of in vivo molecular probe based on xenon / phosphorus multi-nuclear magnetic resonance includes the following steps:

[0057] Step 1: Obtain the corresponding curve between the pH value of the saturated solution of A and the saturated concentration of A , get 129 The sensitivity distribution diagram S1 of the Xe transceiver integrated coil specifically includes the following steps.

[0058] Step 1.1. Obtain a series of pH values ​​of saturated solutions of A. elegans and the corresponding saturated concentrations of A. elegans, and draw a corresponding curve between the pH value of the saturated solutions of A. elegans and the saturated concentrations of A. . Figure 2This is a corresponding curve diagram between pH value and saturation concentration of A.

[0059] Step 1.2: Get a uniform 129 Xe gas phantom package 129 Xe transceiver surface coil 129 Xe gas imaging 29 Sensitivity distribution diagram S1 of the Xe transceiver integrated surface coil. Figure 3 for 129 Schematic diagram of the sensitivity distribution of the Xe transceiver surface coil.

[0060] Step 2: Obtaining the proton magnetic resonance imaging of the brain area of ​​the test subject , specifically including the following steps:

[0061] Obtaining a proton magnetic resonance structural image of the brain region of the subject of examination by performing a proton magnetic resonance scan on the subject of examination in a magnetic resonance imaging device magnet. H .

[0062] Step 3: Obtain 3D image of the brain area of ​​the detected object 31 P chemical shift imaging data , get the hole A 129 Xe magnetic resonance signal distribution image The specific steps include:

[0063] Step 3.1: Obtain 3D images of the subject's brain area 31 P chemical shift imaging data 3D 31 P chemical shift imaging data pass 31 P transceiver integrated birdcage coil 101 is obtained.

[0064] Step 3.2: Obtain the acupoints A in the brain area of ​​the test subject, the first calibration tube 102 and the second calibration tube 103. 129 Acupoint A obtained by 3D UTE sequence scanning 129 Xe magnetic resonance signal distribution image . The brain area of ​​the test object, the acupoint A where the first calibration tube 102 and the second calibration tube 103 are located 129 Xe magnetic resonance signal distribution in A 129 Xe magnetic resonance signal distribution image The corresponding position.

[0065] Step 4: Obtain pH distribution image of the brain area of ​​the test subject , as follows:

[0066] Since the chemical shift of inorganic phosphate (Pi) varies with intracellular pH, the 3D 31 Chemical shift imaging data p The chemical shift distribution map of inorganic phosphate (Pi) was obtained by pixel-by-pixel peak fitting. , and then calculate the pH distribution image of the brain area of ​​the detected object pixel by pixel according to the following formula , pH distribution image of the test subject's brain area The pH value of the kth pixel is the chemical shift distribution map of inorganic phosphate (Pi) The pH value corresponding to the k-th pixel.

[0067] ;

[0068] in, Chemical shift distribution of inorganic phosphate (Pi) The value of the kth pixel, Chemical shift distribution of inorganic phosphate (Pi) The pH value corresponding to the k-th pixel.

[0069] Step 5: Obtain the concentration distribution image of the acupoint A in the brain area of ​​the test object . Acupuncture A concentration distribution image It is an important reference indicator for evaluating the in vivo application of acupuncture A. This parameter directly affects the evaluation of the detection limit of acupuncture A in the brain area of ​​the test subject. The details are as follows:

[0070] Step 5.1, as Figure 5 As shown, the acupoint A including the brain area of ​​the test subject, the first calibration tube 102 and the second calibration tube 103 obtained in step 3.2 is 129 Xe MRI signal distribution Superimpose the pH distribution image of the brain area of ​​the test subject obtained in step 4 superior. I Xe It can reflect the distribution of the first calibration tube 102, the second calibration tube 103 and the brain acupoint A, so I Xe After superimposing the pH distribution image, the pH value of the brain acupoint A distribution can be obtained. Then, according to the brain proton magnetic resonance image obtained in step 2, Confirm the coordinates of the acupoint A in the brain area of ​​the test object , we can get the position coordinates of the acupoint A in the brain area of ​​the detected object pH value at .

[0071] Step 5.2: Obtain the corresponding curve between the pH value of the saturated solution of A and the saturated concentration of A according to step 1.1. The coordinates of the acupoint A in the brain region of the test subject obtained in step 5.1 are pH value of A at the , the position coordinates of the acupoint A in the brain area of ​​the detection object are calculated pixel by pixel using the following formula: The concentration distribution of A in the hole .

[0072] ;

[0073] in is the concentration of a saturated solution of A with a pH of 7.4, The coordinates of the acupoint A in the brain area of ​​the detected object The pH value at for The corresponding saturation concentration of A.

[0074] Step 6: Calculate the coordinates of the Acupoint A in the brain area of ​​the test subject A and 129 Apparent binding rate of Xe , specifically including the following steps:

[0075] Step 6.1: The sensitivity distribution of the surface coil is uneven. 129 The sensitivity distribution diagram S1 of the Xe transceiver surface coil is obtained in step 3. 129 Xe magnetic resonance signal distribution image Signal correction is performed based on the following formula,

[0076] ;

[0077] in, A is the corrected acupoint A 129 Xe magnetic resonance signal distribution image I C The value of the j-th voxel, A 129 Xe magnetic resonance signal distribution image The value of the j-th voxel, for 129 The value of the jth voxel in the sensitivity distribution map S1 of the Xe transceiver integrated surface coil.

[0078] Step 6.2: Calculate the coordinates of the acupoint A in the brain area of ​​the test subject A and 129 Apparent binding rate of Xe ,

[0079] A and 129 Apparent binding rate of Xe Is the effect of the acupoint A in the in vivo experiment129 An important factor for Xe signal intensity, the corrected Xe A 129 Xe magnetic resonance signal distribution image I C The average signal value of the first calibration tube area and the average signal of the second calibration tube area The following relations are satisfied:

[0080] ;

[0081] in, is the concentration of the saturated solution of A in the first calibration tube 102, is the concentration of the saturated solution of A in the second calibration tube 103, Acupoint A and Acupoint B of the first calibration tube area 129 X apparent binding rate, Acupoint A and Acupoint B of the second calibration tube area 129 X apparent binding rate, is the volume of the saturated solution of A in the first calibration tube 102 and the second calibration tube 103.

[0082] Acupuncture A is delivered to the brain through atomization or inhalation. The delivery path is long and there is loss, resulting in the volume of Acupuncture A delivered to the brain being , is the volume of the saturated solution of A delivered to the test subject, To improve the delivery efficiency of Xenon A to the brain, the brain environment is complex and unknown. The gaps in the multi-nuclear molecular probe that could originally bind to xenon will be occupied by other small biological molecules, resulting in the interaction between Xenon A and the brain. 129 X apparent binding rate Changes occur, so the detection of the subject's brain area A and 129 The apparent binding rate X is expressed as Since the hole A in the sample tube is in a pure solution environment, the cavity inside the molecular probe will not be occupied by other substances and can efficiently combine with Xe atoms. Therefore, the hole A in the first calibration tube area is 129 X apparent binding rate , the second calibration tube area A and 129 X apparent binding rate .

[0083] Corrected Acupoint A 129 Xe magnetic resonance signal distribution image I C The coordinates of the acupoint A in the brain area of ​​the detected object Signal distribution at The following relations are satisfied:

[0084] ;

[0085] in, The coordinates of the acupoint A in the brain area of ​​the detected object The concentration distribution of A at the acupoint V0 is the coordinate of the brain area of ​​the detected object. The pixel volume of the hole A at The coordinates of the acupoint A in the brain area of ​​the detected object A and 129 The apparent binding rate of Xe is proportional to ∝.

[0086] A-anime 129 The Xe magnetic resonance signal intensity and the amount of A are linearly related, such as Figure 6 As shown, the corrected acupoint A 129 Xe magnetic resonance signal distribution image I C The average signal value of the first calibration tube area and the average signal of the second calibration tube area , the concentration of A in the first calibration tube 102 and the second calibration tube 103 is set and , and the volume V of the acupuncture A solution in the first calibration tube 102 and the second calibration tube 103 can be linearly fitted to obtain the acupuncture A 129 The relationship between the Xe magnetic resonance signal S and the amount n of acupuncture A is as follows:

[0087] ;

[0088] like Figure 6 As shown, according to the position coordinates of the acupoint A in the brain area of ​​the detected object The distribution of A signal at the , the coordinates of the location of acupoint A in the brain area of ​​the test object The concentration distribution of A in the hole Available 、 Substituting the linear fitting relationship into the acupoint A position coordinates of the brain area of ​​the test object can be obtained. A and 129 Apparent binding rate of Xe as follows:

[0089] ;

[0090] Among them, V0 is the position of the molecular probe in the detection area of ​​the detection object V is the volume of the molecular probe solution in the first calibration tube 102 and the second calibration tube 103, is the concentration of the molecular probe saturated solution in the first calibration tube 102, is the concentration of the molecular probe saturated solution in the second calibration tube 103 .

[0091] The area to be tested in the method of this embodiment is not limited to the brain area of ​​the test subject, but can also be other areas to be tested of the test subject, such as the lungs, heart, kidneys, etc. The molecular probe of this embodiment is not limited to Acupuncture A, but can also be a functional substance such as Zeolitic imidazolate framework-8.

[0092] In vivo A (molecular probe) and 129 The X apparent binding rate distribution can reflect the in vivo delivery efficiency and occupancy of the probe by small biomolecules, effectively guiding the structural improvement of multi-core molecular probes. The in vivo concentration distribution of the probe and the in vivo signal distribution of the probe can qualitatively assess the detection limit (i.e., the detection concentration threshold) of the multi-core molecular probe for in vivo imaging. This information will further guide the structural design of multi-core molecular probes and the improvement of experimental methods.

[0093] Those skilled in the art will understand that all or part of the processes in the above-mentioned embodiment methods can be implemented by instructing related hardware through a computer program. The computer program can be stored in a non-volatile computer-readable storage medium. When the computer program is executed, it can include the processes of the embodiments of the above-mentioned methods.

[0094] Example 2:

[0095] In this embodiment, a computer device is further provided, including a memory and a processor. The memory stores a computer program, and the processor implements the steps in the above embodiment 1 when executing the computer program.

[0096] Example 3:

[0097] In this embodiment, a computer-readable storage medium is provided, on which a computer program is stored. When the computer program is executed by a processor, the steps in the above-mentioned embodiment 1 are implemented.

[0098] Example 4:

[0099] In this embodiment, a computer program product is provided, including a computer program. When the computer program is executed by a processor, the steps in the above-mentioned embodiment 1 are implemented.

[0100] It should be noted that the embodiments described herein are merely illustrative of the spirit of the present invention. Persons skilled in the art may make various modifications, additions, or substitutions to the described embodiments without departing from the spirit of the present invention or exceeding the scope of the appended claims.

Claims

1. A quantitative evaluation method for in vivo molecular probes based on xenon / phosphorus multi-nuclear magnetic resonance, characterized in that: The following steps are involved: Step 1: Obtain the corresponding curve between the pH value of the molecular probe saturated solution and the molecular probe saturation concentration , get 129 Sensitivity distribution diagram S1 of the Xe transceiver integrated coil; Step 2: Obtain a proton magnetic resonance image of the target area. ; Step 3: Get the 3D image of the area to be tested 31 P chemical shift imaging data , obtain molecular probes 129 Xe magnetic resonance signal distribution image ; Step 4. Based on 3D 31 P chemical shift imaging data Generate pH distribution image of the test area of ​​the test object ; Step 5: Proton magnetic resonance imaging of the target area based on the target area Confirm the position coordinates of the molecular probe in the area to be tested , based on molecular probes 129 Xe magnetic resonance signal distribution image and pH distribution image of the test area of ​​the test object Generate a molecular probe concentration distribution image in the target area ; Step 6: Based on the sensitivity distribution map S1, the molecular probe 129 Xe magnetic resonance signal distribution image Perform signal correction and calculate the position coordinates of the molecular probe in the detection area of ​​the detection object Molecular probes at 129 Apparent binding rate of Xe .

2. The quantitative evaluation method based on xenon / phosphorus multi-nuclear magnetic resonance in vivo molecular probe according to claim 1, characterized in that: The corresponding curve between the pH value of the molecular probe saturated solution and the molecular probe saturation concentration in step 1 is generated based on the following steps: Obtain a series of pH values ​​of molecular probe saturated solutions with different pH values ​​and the corresponding molecular probe saturation concentrations, and draw the corresponding curve between the pH value of the molecular probe saturated solution and the molecular probe saturation concentration .

3. The quantitative evaluation method based on xenon / phosphorus multi-nuclear magnetic resonance in vivo molecular probe according to claim 1, characterized in that: In step 1 129 The sensitivity distribution diagram S1 of the Xe transceiver coil is generated based on the following steps: Get a uniform 129 Xe gas phantom package 129 Xe transceiver surface coil 129 Xe gas imaging 129 Sensitivity distribution diagram S1 of the Xe transceiver integrated surface coil.

4. The quantitative evaluation method based on xenon / phosphorus multi-nuclear magnetic resonance in vivo molecular probe according to claim 1, characterized in that: The molecular probe in step 3 129 Xe magnetic resonance signal distribution image Generated based on the following steps: Step 3.1: Get the 3D image of the area to be tested 31 P chemical shift imaging data Sp; Step 3.2: Collect the molecular probes in the test area of ​​the test object, the first calibration tube (102) and the second calibration tube (103). 129 Molecular probes obtained by 3D UTE sequence scanning with Xe 129 Xe magnetic resonance signal distribution image .

5. The quantitative evaluation method based on xenon / phosphorus multi-nuclear magnetic resonance in vivo molecular probe according to claim 1, characterized in that: The pH distribution image of the detection area of ​​the detection object in step 4 Generated based on the following steps: The 3D obtained from step 3 31 Chemical shift imaging data p The chemical shift distribution map of inorganic phosphate was obtained by pixel-by-pixel peak fitting. , and then calculate pixel by pixel according to the following formula to obtain the pH distribution image of the test area of ​​the detection object , pH distribution image of the test subject's brain area The pH value of the kth pixel is the chemical shift distribution map of inorganic phosphate (Pi) The pH value corresponding to the k-th pixel, ； in, Chemical shift distribution of inorganic phosphate The value of the kth pixel, Chemical shift distribution of inorganic phosphate The pH value corresponding to the k-th pixel.

6. The quantitative evaluation method based on xenon / phosphorus multi-nuclear magnetic resonance in vivo molecular probe according to claim 1, characterized in that: The molecular probe concentration distribution image in the test area in step 5 Obtained based on the following steps: Step 5.1: The molecular probe obtained in step 3 129 Xe MRI signal distribution The pH distribution image of the test area of ​​the test object obtained in step 4 is superimposed The pH value of the molecular probe distribution in the test area of ​​the test object is obtained, and then the hydrogen proton magnetic resonance structure image of the test area of ​​the test object obtained in step 2 is obtained. Confirmed molecular probe position coordinates in the area to be tested , get the position of the molecular probe in the detection area of ​​the detection object pH value at ; Step 5.2: The corresponding curve between the pH value of the molecular probe saturated solution and the molecular probe saturation concentration obtained in step 1 is obtained. The position of the molecular probe in the target area is obtained in step 5.

1. pH value at , calculate pixel by pixel to obtain the position of the molecular probe in the area to be tested Concentration distribution at , ； in, is the concentration of the molecular probe saturated solution at pH 7.4, The position of the molecular probe in the area to be tested The pH value at for The corresponding molecular probe saturation concentration.

7. The quantitative evaluation method based on xenon / phosphorus multi-nuclear magnetic resonance in vivo molecular probe according to claim 1, characterized in that: The sensitivity distribution diagram S1 in step 6 is for the molecular probe 129 Xe magnetic resonance signal distribution image Signal calibration is performed based on the following steps: Based on the results obtained in step 1 129 Sensitivity distribution diagram of Xe transceiver surface coil S1 for the molecular probe obtained in step 3 129 Xe magnetic resonance signal distribution image Perform signal correction to obtain the corrected molecular probe 129 Xe magnetic resonance signal distribution image I C The average signal value of the first calibration tube area , the average signal value of the second calibration tube area and the position coordinates of the molecular probe in the detection area of ​​the detection object Signal distribution at , the correction formula is as follows: ； in, For the calibrated molecular probe 129 Xe magnetic resonance signal distribution image The value of the j-th voxel, Molecular probes 129 Xe magnetic resonance signal distribution image The value of the j-th voxel, for 129 Sensitivity distribution of the Xe transceiver surface coil The value of the j-th voxel; The position coordinates of the molecular probe in the detection area of ​​the object to be detected in step 6 Molecular probes at 129 Apparent binding rate of Xe Obtained based on the following steps: The position coordinates of the molecular probe in the detection area of ​​the detection object Molecular probes at 129 Apparent binding rate of Xe The calculation is based on the following formula: ； in, The molecular probe position of the detection object is The pixel volume, is the volume of the molecular probe solution in the first calibration tube (102) and the second calibration tube (103), is the concentration of the molecular probe saturated solution in the first calibration tube (102), is the concentration of the saturated solution of the molecular probe in the second calibration tube (103).

8. A computer device comprising a memory and a processor, wherein the memory stores a computer program, wherein: When the processor executes the computer program, each step of the quantitative evaluation method of the xenon / phosphorus multi-nuclear magnetic resonance in vivo molecular probe according to any one of claims 1 to 7 is implemented.

9. A computer-readable storage medium having a computer program stored thereon, characterized in that: When the computer program is executed by a processor, each step of the quantitative evaluation method of an in vivo molecular probe based on xenon / phosphorus multi-nuclear magnetic resonance is implemented according to any one of claims 1 to 7.

10. A computer program product comprising a computer program, characterized in that When the computer program is executed by a processor, each step of the quantitative evaluation method of an in vivo molecular probe based on xenon / phosphorus multi-nuclear magnetic resonance is realized according to any one of claims 1 to 7.

Images