Relaxation exchange magnetic resonance imaging (REXI) sequence, acquisition and analysis method, and use thereof in measuring transmembrane transport of cerebrospinal fluid

Abstract

Provided in the present invention is a relaxation exchange magnetic resonance imaging (REXI) sequence, comprising: a filtering module, consisting of a 90° excitation radio frequency pulse and a 180° refocusing radio frequency pulse; an exchange module, consisting of a 90° excitation radio frequency pulse and an exchange delay; and a detection module, consisting of a 90° excitation radio frequency pulse and a plurality of 180° refocusing radio frequency pulses. Paired crusher gradient pulses are applied to the filtering module and the detection module, and a spoiler gradient pulse is applied to the exchange module. Further disclosed in the present invention is an acquisition and analysis method for the REXI sequence: during REXI acquisition, the echo time of the filtering module is fixed, and only the exchange delay time of the exchange module and the echo time of the detection module are changed; and during REXI analysis, a dual-chamber exchange model is used for fitting data. Further disclosed in the present invention is the use of the REXI sequence and the acquisition and analysis method thereof in measuring transmembrane transport of cerebrospinal fluid by magnetic resonance imaging, which is especially suitable for magnetic resonance imaging for rapidly measuring the speed of molecular exchange between a short T2 component and a long T2 component in a dual-component system.

Description

A relaxation exchange magnetic resonance imaging (REXI) sequence, acquisition and analysis method, and its application in measuring transmembrane transport of cerebrospinal fluid. Technical Field

[0001] This invention relates to the field of magnetic resonance imaging, and in particular to a relaxation exchange magnetic resonance imaging REXI sequence, acquisition and analysis method, and its application in measuring transmembrane transport of cerebrospinal fluid. Background Technology

[0002] Molecular exchange between different components occurs extensively in porous media, including rocks, cement, and most biological tissues. In brain tissue, water molecule exchange occurs between different biological components, such as intracellular and extracellular spaces, cerebrospinal fluid and brain parenchyma, and choroid plexus and cerebrospinal fluid, and is crucial for maintaining brain water homeostasis. Therefore, quantitative measurement of the water molecule exchange rate is an important means of characterizing the physical properties of porous media or the function and state of biological tissues.

[0003] Nuclear magnetic resonance (NMR) spectrometry and magnetic resonance imaging (MRI) are the main tools for measuring the exchange rates of water molecules in different components. For two-component or multi-component systems with different diffusion coefficients, (1) diffusion exchange spectroscopy NMR sequences and methods have been developed [Galvosas, P., et al. (2007). Magnetic Resonance Imaging, 25(4), 497-500.], which are widely used for the physical characterization of porous media such as polymer materials; (2) filtered exchange imaging MRI sequences and analysis methods with imaging capabilities [Bai, R., et al. (2020). NeuroImage, 219(May), 117039.], which have been initially applied to the functional imaging of tumors and brain tissues.

[0004] For two-component or single-component systems with different transverse relaxation times (T2), relaxation exchange spectroscopy (REXSY) nuclear magnetic resonance technology has been developed [Dortch, RD, et al. (2009). Journal of Chemical Physics, 131(16), 1-11.] and applied to the physical characterization of porous media such as ores. In biological tissues, two-component or multi-component systems with different transverse relaxation times (T2) are abundant. Choroid plexus tissue-cerebrospinal fluid (CSF) and brain parenchyma-CSF are two typical two-T2 component systems in brain tissue. The transverse relaxation time (T2) of water molecules in CSF is much longer than that in choroid plexus tissue or brain parenchyma. The rate of water molecule exchange between the two components of choroid plexus tissue-CSF is crucial for characterizing choroid plexus function, while the rate of water molecule exchange between the two components of brain parenchyma-CSF is an important indicator of CSF circulation efficiency. For exchange measurements of components with different transverse relaxation times (T2) in biological tissues, imaging capabilities and rapid acquisition are often required. However, REXSY is a nuclear magnetic resonance spectroscopy method that lacks imaging capabilities and is a three-dimensional acquisition sequence with excessively long acquisition times, failing to meet the needs of in vivo imaging. Therefore, for exchange measurements of two-component or multi-component systems with different transverse relaxation times (T2), there is currently a lack of rapid magnetic resonance imaging methods with imaging capabilities suitable for in vivo biological applications. Summary of the Invention

[0005] The purpose of this invention is to provide a relaxation exchange magnetic resonance imaging REXI sequence and its acquisition and analysis method, as well as its application in magnetic resonance imaging for measuring transmembrane transport of cerebrospinal fluid. It is suitable for magnetic resonance imaging to rapidly measure the molecular exchange rate between the short T2 component and the long T2 component in a two-component system.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] A relaxation-exchange magnetic resonance imaging (REXI) sequence, the REXI sequence comprising: a filtering module including a first 90° excitation radio frequency pulse and a first 180° refocusing radio frequency pulse; an exchange module including a second 90° excitation radio frequency pulse; a detection module including a third 90° excitation radio frequency pulse and multiple second 180° refocusing radio frequency pulses; applying paired crusher gradient pulses to the filtering module and the detection module; and applying a spoiler gradient pulse to the exchange module.

[0008] The execution methods of the REXI sequence include:

[0009] S1. Apply a first 90° excitation radio frequency pulse, and then apply a first 180° refocusing radio frequency pulse;

[0010] S2, Apply a breaking gradient pulse;

[0011] S3. Apply a second 90° excitation radio frequency pulse;

[0012] S4. Apply a spoiler gradient pulse;

[0013] S5. Apply the third 90° excitation radio frequency pulse;

[0014] S5. Apply a breaking gradient pulse;

[0015] S6. Apply a second 180° refocusing radio frequency pulse and perform magnetic resonance imaging K-space acquisition;

[0016] The interval between the first 90° excitation RF pulse and the second 90° excitation RF pulse is the echo time TE of the filtering module. f The interval between the first 90° excitation RF pulse, the second 90° excitation RF pulse, and the first 180° refocusing RF pulse is TE. f / 2; The interval between the second 90° excitation RF pulse and the third 90° excitation RF pulse is the exchange time t. m The interval between each second 180° refocusing RF pulse is the detection module echo time TE. d The interval between the third 90° excitation RF pulse and the first 180° refocusing RF pulse in the second 180° refocusing RF pulse is TE. d / 2.

[0017] S6 can be repeated multiple times as needed.

[0018] In steps S2 and S4, the amplitude of the breakup gradient pulse is calculated based on the desired breakup gradient dispersion: φ c =γG c t c Δz

[0019] In the formula, φ c The phase is a fragmented gradient dispersed phase, γ is the gyromagnetic ratio, and G is the gyromagnetic ratio. c Let t be the magnitude of the breaking gradient. c Let be the duration of the breaking gradient, which is applied in the Z direction. Δz is the voxel size in the Z direction. Within a horizontally placed master magnet, the Z direction is defined as the direction pointing towards the observer. The X direction is from left to right. The Y direction is from bottom to top.

[0020] In step S5, the amplitude of the perturbation gradient pulse is calculated based on the desired perturbation gradient dephasing: φ s =γG s t s Δr

[0021] In the formula, φ s For the perturbation gradient phase dispersion, γ is the gyromagnetic ratio, and G is the perturbation gradient s Let t be the amplitude of the perturbation gradient. s The duration of the perturbation gradient is given. The perturbation gradient is applied in any one of the X, Y, and Z directions. Δr is the voxel size in the selected direction. In a horizontally placed main magnet, the Z direction is defined as the direction pointing towards the observer, the Y direction is the direction from bottom to top, and the X direction is the direction from left to right.

[0022] In step S6, the magnetic resonance imaging K-space acquisition can be EPI fast imaging or other spatial coding methods.

[0023] This invention also discloses the application of the aforementioned REXI sequence in magnetic resonance imaging. The application is for measuring transmembrane transport of cerebrospinal fluid using magnetic resonance imaging. Further, the application is for measuring the molecular exchange rate between the short T2 component and the long T2 component in a two-component system using magnetic resonance imaging. Still further, the application is for measuring the water molecule exchange rate at the choroid plexus (short T2 component)-cerebrospinal fluid (long T2 component) interface or the water molecule cross-barrier exchange rate at the cerebrospinal fluid (long T2 component)-brain parenchyma (short T2 component) interface.

[0024] The present invention also provides a method for acquiring and analyzing the above-mentioned REXI sequences, the method comprising:

[0025] (1) Using multi-layer multi-echo MSME sequences at different echo times TE eq The magnetic resonance signal S was acquired below. eq ;

[0026] (2) Using the relaxation exchange imaging REXI sequence, the filtering module TE f Set to a fixed value, at different exchange times t m Echo time (TE) of different detection modules d Acquiring magnetic resonance imaging signals S(t) m ,TE d );

[0027] (3) Using the magnetic resonance signal S acquired in step (1) eq Fit the proportion of short T2 components under equilibrium conditions Transverse relaxation time T2 of the short T2 component short Transverse relaxation time T2 of the T2 component longand the initial signal S0;

[0028] (4) Using the magnetic resonance signal S(t) acquired in step (2) m ,TE d ) and step (3) T2 short and T2 long Fit different exchange times t m The proportion of short T2 components f short (t m );

[0029] (5) Using step (3) and f in step (4) short (t m The apparent water molecule exchange rate k was obtained by fitting the data.

[0030] (6) Using step (3) The apparent water molecule exchange rate k in step (5) is corrected to obtain the short T2 component water molecule outflow rate constant k. sl .

[0031] The magnetic resonance sequence provided by this invention employs relaxation-based exchange-weighted imaging: during REXI acquisition, the echo time of the filtering module is fixed, while only the exchange delay time of the exchange module and the echo time of the detection module are changed; in REXI analysis, a dual-chamber exchange model is used to fit the data; specifically, the least squares method is used to fit the magnetic resonance signals under different exchange times, and combined with the short T2 component proportion parameter, the apparent water molecule exchange rate and the short T2 component water molecule outflow rate constant are obtained.

[0032] Preferably, in steps (1) and (2): the readout scheme of the detection module in the MSME sequence and REXI sequence can be changed to the planar echo imaging (EPI) acquisition encoding method to speed up the imaging speed; the detection module can combine multi-shot EPI and multi-band EPI technology (while using multi-layer SMS technology) to simultaneously achieve the requirements of short TE and multi-layer fast scanning.

[0033] Preferably, the magnetic resonance imaging method further includes preprocessing (motion correction, etc.) of the MSME and REXI sequence images.

[0034] The echo time of the filtering module and the echo time of the detection module are fixed; only the switching delay time of the switching module is changed.

[0035] Preferably, the filtering module TE in step (2) f The parameter is generally set to more than twice the short T2 in a dual-T2 component system.

[0036] Preferably, in step (3), according to the formula

[0037] More preferably, f can be adjusted according to the difference in T1 between the short-T2 component and the long-T2 component. short (t m Correction is then performed. Preferably, in step (4), the correction is performed according to the formula... Fitting, substituting the T2 obtained in the previous step short and T2 long The different exchange times t were obtained by fitting. m The proportion of short T2 components f short (t m ), where S(t) m ,TE d ) is in the REXI detection module at different t m Multi-echo acquisition (TE) d The magnetic resonance signal obtained by this formula, along with the initial signal S0(t), is also obtained by fitting the magnetic resonance signal. m ).

[0038] Preferably, in step (5), according to the formula Fitting; the apparent water molecule exchange rate (k) was obtained by fitting using the least squares method. Among them, The percentage of components in the instantaneous short T2 phase after the filter module is applied, obtained from the fitting process.

[0039] Preferably, in step (6), according to the formula The apparent water molecule exchange rate is corrected.

[0040] The exchange rate between the short T2 component and the long T2 component is the choroid plexus-cerebrospinal fluid water molecule exchange rate or the cerebrospinal fluid-brain parenchyma exchange interface water molecule cross-barrier exchange rate. Then the water molecule outflow rate constant of the short T2 component is the choroid plexus water molecule outflow rate constant or the brain parenchyma water molecule outflow rate constant.

[0041] In the above method, when used for magnetic resonance imaging of the exchange rate between short T2 components and long T2 components in different tissues, the echo time TE of the detection module of the relaxation exchange imaging REXI sequence can be adjusted as needed. d Exchange time t m And the echo time of the filtering module.

[0042] This invention also provides an application of the above-mentioned acquisition and analysis method in magnetic resonance imaging (MRI). The application is for measuring transmembrane transport of cerebrospinal fluid (CSF) using MRI. Further, the application is for measuring the molecular exchange rate between the short-T2 component and the long-T2 component in a two-component system using MRI. Still further, the application is for measuring the water molecule exchange rate at the choroid plexus (short-T2 component)-CSF (long-T2 component) interface or the water molecule cross-barrier exchange rate at the CSF (long-T2 component)-brain parenchyma (short-T2 component) interface.

[0043] Compared with the prior art, the present invention has the following superior effects:

[0044] The relaxation exchange magnetic resonance imaging (REXI) sequence and its acquisition and analysis method provided by this invention are applicable to the magnetic resonance imaging measurement of water molecule exchange rate in a T2 two-component system, using a fixed filter module TE. f The parameters were changed from the existing three-dimensional acquisition of relaxation exchange nuclear magnetic resonance spectroscopy (REXSY) to two-dimensional acquisition of relaxation exchange magnetic resonance imaging (REXI), which greatly improved the acquisition speed of water molecule exchange rate magnetic resonance imaging measurement.

[0045] The relaxation exchange magnetic resonance imaging REXI sequence and its acquisition and analysis method provided by this invention have spatial imaging capabilities and can provide the spatial distribution of water molecule exchange rate in the T2 two-component system. Attached Figure Description

[0046] Figure 1 is a schematic diagram of a REXI sequence used in this invention;

[0047] Figure 2 is a flowchart of the magnetic resonance imaging method for measuring the exchange rate of water molecules between the choroid plexus and cerebrospinal fluid using REXI sequences in Example 1.

[0048] Figure 3 shows REXI images at different exchange times in Example 1;

[0049] Figure 4 shows the percentage of choroid plexus tissue f fitted in Example 1. short (t m Regarding t m The curve;

[0050] Figure 5 shows the fitted curve in Example 1 and the corrected efflux rate constant k of water molecules from the vesicle cluster. sl ;

[0051] Figure 6 shows the structural image of the rat brain in Example 2, and the choroid plexus of the region of interest (ROI) delineated on the structural image. Detailed Implementation

[0052] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0053] The REXI sequence used in this invention is shown in Figure 1. This sequence comprises three modules: a filter block, a mixing time, and a detection block. Both the filter and detection modules use spin echo sequences. Taking the measurement of the water molecule exchange rate between the choroid plexus (short T2 component) and cerebrospinal fluid (long T2 component) as an example, the function of each module is explained: the filter block is used to filter (suppress) the magnetization vector of the choroid plexus water molecules. This is achieved by setting an appropriate filter block echo time, TE. f The signal is suppressed in the choroid plexus tissue while avoiding significant impact on the cerebrospinal fluid signal. The exchange module can change the transverse magnetization vector to the longitudinal direction for storage. In the exchange module, water molecules in the choroid plexus and water molecules in the cerebrospinal fluid are exchanged. The filtered (suppressed) water molecules can recover the signal through cross-barrier water exchange, and the degree of recovery varies with the exchange time (t). m The detection module uses multi-echo acquisition to quantify the proportion of exchanged and unexchanged water molecules, and can detect the percentage of water molecules that have undergone t... m Magnetic resonance signal after time-exchange; pairwise crusher gradient (G) used for coherent path selection c ( ) can replace phase cycling to shorten acquisition time; spoiler gradient (G s This is used to remove residual transverse magnetization vectors. To increase the image signal-to-noise ratio and remove inflow effects, the pulses in the filtering module are all non-selective pulses; the pulses in the detection module are layer-selective pulses.

[0054] Specifically, the filtering module consists of a 90° excitation RF pulse (first 90° excitation RF pulse) and a 180° refocusing RF pulse (first 180° refocusing RF pulse). The interval between the 90° excitation RF pulse (first 90° excitation RF pulse) and the 180° refocusing RF pulse (first 180° refocusing RF pulse) of the filtering module is TE. f / 2, the interval between the 180° refocusing RF pulse (first 180° refocusing RF pulse) of the filtering module and the subsequent 90° excitation RF pulse (second 90° excitation RF pulse) in the switching module is TE. f / 2; The switching module consists of a 90° excitation RF pulse (second 90° excitation RF pulse), and the interval between this 90° excitation RF pulse (second 90° excitation RF pulse) and the subsequent 90° excitation RF pulse in the detection module (third 90° excitation RF pulse) is the switching time (t). m The detection module consists of one 90° excitation RF pulse (the third 90° excitation RF pulse) and multiple 180° refocusing RF pulses (the second 180° refocusing RF pulse). The interval between each 180° refocusing RF pulse in the detection module is the echo time (TE) of the detection module. d In the detection module, the interval between the 90° excitation RF pulse (the third 90° excitation RF pulse) and the first 180° refocusing RF pulse (the second 180° refocusing RF pulse) is TE / 2. Each 180° refocusing RF pulse in the detection module generates an echo signal after TE / 2, which is used to fill the K-space data of the magnetic resonance imaging (MRI) and ultimately reconstruct the MRI image.

[0055] Subsequently, based on the desired fragmentation gradient dispersion, the fragmentation gradient pulses in the filtering and detection modules are calculated. The fragmentation gradient consists of two pulses applied in the same direction (Z direction) with a duration (t). c ) and amplitude (G c The gradients are all identical, with the first breaking gradient applied before the 90° excitation RF pulse of the switching module and the second breaking gradient applied after the 90° excitation RF pulse of the detection module. This is to generate the desired breaking gradient dephasing (φ). c ), which needs to satisfy the following relationship: φ c =γG c t c Δz

[0056] Where Δz is the voxel size in the Z direction, and within a horizontally placed main magnet, the Z direction is defined as the direction pointing towards the observer. The X direction is from left to right. The Y direction is from bottom to top. Empirically, the minimum φ... c It usually satisfies a value greater than or equal to 4π.

[0057] Then, based on the desired phase gradient dephasing, the phase gradient pulse in the switching module is calculated. The phase gradient can be applied individually in the X, Y, or Z directions, or simultaneously in all three directions. In this embodiment 1, the phase gradient is applied in the Z direction. The amplitude of the phase gradient is G. s The duration is t sTo generate the desired perturbation gradient dephasing (φ) s ), which needs to satisfy the following relationship: φ s =γG s t s Δr

[0058] Where Δr is the voxel size in the selected direction, typically set to φ. s Greater than or equal to 8π.

[0059] Therefore, the execution methods of REXI sequences include:

[0060] S1. Apply a first 90° excitation radio frequency pulse, and then apply a first 180° refocusing radio frequency pulse;

[0061] S2, Apply a breaking gradient pulse;

[0062] S3. Apply a second 90° excitation radio frequency pulse;

[0063] S4. Apply a phase-disrupting gradient pulse;

[0064] S5. Apply the third 90° excitation radio frequency pulse;

[0065] S5. Apply a breaking gradient pulse;

[0066] S6. Apply a second 180° refocusing radio frequency pulse and perform magnetic resonance imaging K-space acquisition.

[0067] Example 1

[0068] As a specific embodiment, the REXI sequence provided above is used for magnetic resonance imaging to measure the water molecule exchange rate between the choroid plexus (short T2 component) and cerebrospinal fluid (long T2 component). That is, the REXI sequence provided by this invention is applied to the brain of Wistar Kyoto rats for magnetic resonance imaging to measure the water molecule exchange rate between the choroid plexus and cerebrospinal fluid. The acquisition and analysis flowchart is shown in Figure 2, and specifically includes the following steps:

[0069] Step 1: The anesthetized rats were placed in a 9.4T magnetic resonance imaging system, and single-slice images were acquired with the center of the lateral ventricle as the scanning center point. In this example, magnetic resonance data were acquired from 8 rats.

[0070] Step 2: Set the MSME sequence to a resolution of 0.27 × 0.36 mm. 2 The slice thickness was 1.5 mm, and single-slice acquisition was used. The number of echoes was 30, and the echo times were 7, 14, 21, ..., 203, 210 ms. The sequence repetition time (TR) was 2500 ms, obtaining the imaging results of the MSME sequence (magnetic resonance signal S). eq ).

[0071] Step 3: Set the REXI sequence to a resolution of 0.27 × 0.36 mm. 2 The layer thickness is 1.5mm, and single-layer acquisition is used. The fixed filter module echo time should be set to 30ms. The detection module is set to multi-echo detection, with 30 echoes and echo times of 7, 14, 21, ... 203, 210ms. The switching module is set to four different switching times (t). m The measurements were performed multiple times at intervals of 25ms, 100ms, 200ms, and 400ms. The sequence repetition time (TR) was variable, ranging from 2500ms+t. m Imaging results of REXI sequences were obtained (magnetic resonance signal S(t)). m )).

[0072] In this embodiment, φ c It is usually set to 4π, φ s It is usually set to 8π.

[0073] Step 4: Using the magnetic resonance signal acquired in Step 2, according to the formula... Fit the proportion of choroid plexus tissue in equilibrium state Lateral relaxation time of choroid plexus (T2) short ) and the transverse relaxation time of cerebrospinal fluid (T2) long (and the initial signal S0), where S eq The magnetic resonance signals were obtained from different TE acquisitions.

[0074] Step 5: Utilize the magnetic resonance signal S(t) acquired in Step 3 m The percentage of choroid plexus tissue under equilibrium conditions was obtained by fitting the data in step four. Lateral relaxation time of choroid plexus (T2) short ) and the transverse relaxation time of cerebrospinal fluid (T2) long According to the formula Fit different t m The percentage of choroid plexus tissue f short (t m ), where S(t) m ,TE d ) is the multi-echo acquisition (TE) module of the REXI detection module. d The magnetic resonance signal obtained by this formula, along with the initial signal S0(t), is also obtained by fitting the magnetic resonance signal. m ).

[0075] Step Six: Utilize the choroid plexus tissue percentage in equilibrium obtained in Step Four. The difference between t obtained in step five and t m The percentage of choroid plexus tissue fshort (t m ), for the formula The apparent water molecule exchange rate (k) was obtained by fitting using the least squares method. The instantaneous vesicle cluster fraction after the application of the filtration module was also obtained by fitting.

[0076] Step 7: Utilize the choroid plexus tissue percentage in equilibrium obtained in Step 4. And the apparent water molecule exchange rate (k) obtained in step six, according to the formula The apparent water molecule exchange rate between the choroid plexus and cerebrospinal fluid was corrected to obtain the choroid plexus water molecule outflow rate constant (k). sl ).

[0077] To demonstrate the effectiveness of this embodiment in measuring the rate of water molecule exchange between the choroid plexus and cerebrospinal fluid, the experimental results of this specific embodiment will be described below with reference to the accompanying drawings:

[0078] Taking the results of a single-layer image of a single rat as an example, Figure 3 shows the different exchange times t obtained in step three of this specific embodiment. m The REXI images are shown below. As shown in Figure 3, the lateral ventricles are clearly visible in the REXI images, with signals higher than those of the surrounding tissues, while the lateral ventricles and tissues are difficult to distinguish in the MSME images; this indicates that the REXI filtering module effectively suppresses the tissue signals. Figure 4 illustrates step five in this specific embodiment, where different t values ​​are obtained by fitting the REXI signals. m The percentage of choroid plexus tissue f short (t m ). Observed f short (t m ) with t m The increase indicates that the proportion of plexus tissue has recovered within the exchange module. Figure 5 shows the fitting curve from step six and the plexus water molecule outflow rate constant (k) obtained from step seven. sl This indicates that the fitting formula in step six can handle different t values ​​well. m The percentage of choroid plexus tissue f short (t m By fitting the data, the outflow rate constant of water molecules from the vesicle cluster (k) was finally obtained. sl ).

[0079] In summary, by using the REXI sequence and magnetic resonance imaging method provided by this invention (mainly including bicomponent exponential fitting of transverse relaxation time and component proportion and exchange rate fitting), it is possible to measure the steady-state outflow rate of water molecules from the choroid plexus to the cerebrospinal fluid.

[0080] Example 2

[0081] Based on Example 1, as another possible implementation, the following optional steps can be added to achieve more accurate delineation of regions of interest based on ventricle cluster imaging. The optional steps are as follows:

[0082] Step 1: Set the T2 TurboRare sequence to a resolution of 0.14×0.14×0.5mm. 3 The echo time was set to 8.5 ms, the RARE factor was set to 8, and the repetition time was set to 2200 ms to obtain structural images of the rat brain.

[0083] Step 2: On the high-resolution structural image obtained in Step 1, the region of interest (ROI) of the choroid plexus is delineated, and the ROI image is downsampled to the same resolution as the REXI image using a bilinear interpolation algorithm to obtain the final choroid plexus mask. Figure 6 shows a structural image of the rat brain and the delineation of the ROI choroid plexus on the structural image.

[0084] Step 3: Using the vesicle mask obtained in Step 2, average the MSME or REXI image signal values ​​of all pixels within the mask to perform the parameter analysis shown in Figure 2.

[0085] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A relaxation exchange magnetic resonance imaging REXI sequence, characterized in that, The REXI sequence includes: a filtering module, including a first 90° excitation RF pulse and a first 180° refocusing RF pulse; an exchange module, including a second 90° excitation RF pulse; a detection module, including a third 90° excitation RF pulse and multiple second 180° refocusing RF pulses; paired broken gradient pulses are applied to the filtering module and the detection module; and a phase-scratching gradient pulse is applied to the exchange module.

2. The relaxation exchange magnetic resonance imaging (REXI) sequence of claim 1, wherein, The execution methods of the REXI sequence include: S1. Apply a first 90° excitation radio frequency pulse, and then apply a first 180° refocusing radio frequency pulse; S2, Apply a breaking gradient pulse; S3. Apply a second 90° excitation radio frequency pulse; S4. Apply a phase-disrupting gradient pulse; S5. Apply the third 90° excitation radio frequency pulse; S5. Apply a breaking gradient pulse; S6. Apply a second 180° refocusing radio frequency pulse and perform magnetic resonance imaging K-space acquisition; The interval between the first 90° excitation RF pulse and the second 90° excitation RF pulse is the echo time TE of the filtering module. f The interval between the first 90° excitation RF pulse, the second 90° excitation RF pulse, and the first 180° refocusing RF pulse is TE. f / 2; The interval between the second 90° excitation RF pulse and the third 90° excitation RF pulse is the exchange time t. m The interval between each second 180° refocusing RF pulse is the detection module echo time TE. d The interval between the third 90° excitation RF pulse and the first 180° refocusing RF pulse in the second 180° refocusing RF pulse is TE. d / 2.

3. The relaxation exchange magnetic resonance imaging (REXI) sequence of claim 2, wherein, In said steps S2 and S4, the amplitude of the crushing gradient pulse is calculated according to the desired crushing gradient dispersion: φ c = γG c t c Δz In the formula, φ c The phase is a fragmented gradient dispersed phase, γ is the gyromagnetic ratio, and G is the gyromag c Let t be the magnitude of the breaking gradient. c The duration of the breaking gradient is given. The breaking gradient is applied in the Z direction, and Δz is the voxel size in the Z direction. In a horizontally placed main magnet, the Z direction is defined as the direction pointing towards the observer.

4. The relaxation exchange magnetic resonance imaging (REXI) sequence of claim 2, wherein, In step S5, the amplitude of the spoiler gradient pulse is calculated according to the desired spoiler gradient dispersion: φ s = γG s t s Δr In the formula, φ s For the perturbation gradient phase dispersion, γ is the gyromagnetic ratio, and G is the perturbation gradient s Let t be the amplitude of the perturbation gradient. s The duration of the perturbation gradient is given. The perturbation gradient is applied in any one of the X, Y, and Z directions. Δr is the voxel size in the selected direction. In a horizontally placed main magnet, the Z direction is defined as the direction pointing towards the observer, the Y direction is the direction from bottom to top, and the X direction is the direction from left to right.

5. A method of acquisition and analysis of a relaxation exchange magnetic resonance imaging (REXI) sequence, characterized in that, The data collection and analysis methods include: (1) using a multi-slice multi-echo MSME sequence at different echo times TE eq The magnetic resonance signals S are acquired eq ; (2) using the relaxation exchange imaging, REXI, sequence of any of claims 1-4 to acquire magnetic resonance signals S(t f ) with a fixed value set to a different exchange time t m and a different detection module echo time, TE d . m d )​ (3) fitting the magnetic resonance signal S collected in step (1) to a model eq Fitting out the short T2 component proportion fraction in the equilibrium state transverse relaxation time T2 of the short T2 component short transverse relaxation time T2 of the long T2 component long and an initial signal S0; (4) using the magnetic resonance signals S(t m , TE d ) acquired in step (2) and the T2 short and T2 long fitting out the short T2 component proportion fraction f m of different exchange time t short (t m ); (5) using the product of step (3) and f of step (4) short (t m ), the apparent water exchange rate k is fitted. (6) using the product of step (3) The k pair apparent water molecule exchange rates of step (5) are corrected, and finally the short T2 component water molecule efflux rate constant k is obtained sl .

6. The method for acquiring and analyzing relaxation exchange magnetic resonance imaging REXI sequences according to claim 5, characterized in that, In step (3), the formula is fitted.

7. The method for acquiring and analyzing relaxation exchange magnetic resonance imaging REXI sequences according to claim 5, characterized in that, In step (4), the initial signal S0(t) is determined according to the formula fitting; simultaneously fitting results in the initial signal S0(t m ).

8. The method for acquiring and analyzing relaxation exchange magnetic resonance imaging REXI sequences according to claim 5, characterized in that, In step (5), the formula fitting; simultaneously fitting the instantaneous short T2 component after application of the filtration module 9. The method for acquiring and analyzing relaxation exchange magnetic resonance imaging REXI sequences according to claim 5, characterized in that, In step (6), according to the formula The apparent water molecule exchange rate is corrected.

10. The method for acquiring and analyzing relaxation exchange magnetic resonance imaging REXI sequences according to claim 5, characterized in that, The exchange rate between the short T2 component and the long T2 component is the choroid plexus-cerebrospinal fluid water molecule exchange rate or the cerebrospinal fluid-brain parenchyma exchange interface water molecule cross-barrier exchange rate. Then the water molecule outflow rate constant of the short T2 component is the choroid plexus water molecule outflow rate constant or the brain parenchyma water molecule outflow rate constant.

11. The application of the relaxation exchange magnetic resonance imaging REXI sequence according to any one of claims 1-4 and the acquisition and analysis method according to any one of claims 5-10 in the measurement of cerebrospinal fluid transmembrane transport by magnetic resonance imaging.

12. The application according to claim 11, characterized in that, The application is to measure the molecular exchange rate between the short T2 component and the long T2 component in a two-component magnetic resonance imaging system.

13. The application according to claim 12, characterized in that, The application is to measure the rate of water molecule exchange between the choroid plexus and cerebrospinal fluid or the rate of water molecule exchange across the barrier at the cerebrospinal fluid-brain parenchyma exchange interface.

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