Relaxation exchange magnetic resonance imaging REXI sequence, acquisition and analysis method and application of relaxation exchange magnetic resonance imaging REXI sequence in measurement of cerebrospinal fluid transmembrane transport

By using the relaxation exchange magnetic resonance imaging REXI sequence in magnetic resonance imaging, the problem in the existing technology that it is difficult to quickly measure the water molecule exchange rate of a two-component system in biological tissues is solved, and fast, imaging-capable water molecule exchange is achieved. Rate measurement.

CN119335454APending Publication Date: 2025-01-21ZHEJIANG UNIV +1
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Patent Information

Application Number
CN202411453673.2
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-10-17
Publication Date
2025-01-21

AI Technical Summary

Technical Problem

The prior art is difficult to quickly and efficiently measure the rate of water molecules exchange between two-component or multi-component systems with different lateral relaxation times in biological tissues, especially in live imaging, which lacks imaging capabilities and rapid acquisition. Magnetic resonance imaging method.

Method used

The Rexi sequence of relaxation of magnetic resonance imaging is used. This sequence includes filtering modules, exchange modules, and detection modules. By applying specific radio frequency pulses and gradient pulses to achieve rapid measurement of water molecular exchange speed in the dual component system.

Benefits of technology

This method can quickly measure the water molecule exchange rate between the short T2 component and the long T2 component in the two-component system, improves the acquisition speed of magnetic resonance imaging measurements, and has spatial imaging capabilities to provide information on the water molecule exchange rate. spatial distribution.

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Abstract

The invention provides a relaxation exchange magnetic resonance imaging REXI sequence. A filtering module is composed of a 90-degree excitation radio frequency pulse and a 180-degree refocusing radio frequency pulse; the switching module is composed of a 90-degree excitation radio frequency pulse and switching delay; the detection module is composed of a 90-degree excitation radio frequency pulse and a plurality of 180-degree refocusing radio frequency pulses; paired crushing gradient pulses are applied to the filtering module and the detection module; and applying a phase-disturbing gradient pulse to the switching module. The invention further discloses an acquisition and analysis method of the REXI sequence, in REXI acquisition, the echo time of the filter module is fixed, and only the exchange delay time of the exchange module and the echo time of the detection module are changed; and performing REXI analysis, and fitting data by adopting a double-chamber exchange model. The invention also discloses an application of the REXI sequence and the acquisition and analysis method thereof in magnetic resonance imaging measurement of cerebrospinal fluid transmembrane transport, and the REXI sequence is especially suitable for magnetic resonance imaging for rapidly measuring the molecular exchange speed between a short T2 component and a long T2 component in a two-component system.
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Description

Technical Field

[0001] The present invention relates to the technical field of magnetic resonance imaging, and in particular to a relaxation exchange magnetic resonance imaging REXI sequence, an acquisition and analysis method and an application thereof in measuring transmembrane transport of cerebrospinal fluid. Background Art

[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 inside and outside cells, between different biological components such as cerebrospinal fluid and brain parenchyma, and between the choroid plexus and cerebrospinal fluid, and is key to maintaining brain water homeostasis. Therefore, quantitative measurement of water molecule exchange rate is an important means to characterize the physical characteristics of porous media or the function and state of biological tissues.

[0003] Nuclear magnetic resonance spectrometers and magnetic resonance imaging are the main tools for measuring the exchange rate of water molecules of different components. For two-component or multi-component systems with different diffusion coefficients, (1) diffusion exchange spectroscopy nuclear magnetic resonance sequences and methods have been developed [Galvosas, P., et al (2007). Magnetic Resonance Imaging, 25 (4), 497–500.], which are widely used in the physical characterization of porous media such as polymer materials; (2) Filtered exchange imaging magnetic resonance imaging 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, there are a large number of two-component or multi-component systems with different transverse relaxation times T2. Choroid plexus tissue-cerebrospinal fluid and brain parenchyma-cerebrospinal fluid are two typical two-T2 component systems in brain tissue. The transverse relaxation time T2 of water molecules in cerebrospinal fluid is much longer than that of water molecules in choroid plexus tissue or brain parenchyma. The exchange rate of water molecules between the choroid plexus tissue-cerebrospinal fluid is crucial to characterize the function of the choroid plexus, while the exchange rate of water molecules between the brain parenchyma-cerebrospinal fluid is an important indicator for characterizing the circulation efficiency of cerebrospinal fluid. For the exchange measurement of components with different transverse relaxation times T2 in biological tissues, imaging capabilities and fast acquisition are often required. However, REXSY is a nuclear magnetic resonance spectroscopy method that does not have imaging capabilities, and is a three-dimensional acquisition sequence with too long acquisition time to meet the needs of in vivo imaging. Therefore, for the exchange measurement of two-component or multi-component systems with different transverse relaxation times T2, there is still a lack of fast magnetic resonance imaging methods with imaging capabilities for in vivo biological applications. Summary of the invention

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

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

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

[0008] The execution method of the REXI sequence includes:

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

[0010] S2, applying a crushing gradient pulse;

[0011] S3, applying a second 90° excitation radio frequency pulse;

[0012] S4, applying a spoiler gradient pulse;

[0013] S5, applying a third 90° excitation radio frequency pulse;

[0014] S5, applying a crushing gradient pulse;

[0015] S6, applying a second 180° refocusing radio frequency pulse and performing 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 filter module echo time TE f The intervals between the first 90° excitation RF pulse and the second 90° excitation RF pulse and the first 180° refocusing RF pulse are all 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 time 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] Wherein, S6 can be repeated multiple times as needed.

[0018] In the steps S2 and S4, the amplitude of the crushing gradient pulse is calculated according to the desired crushing gradient dephasing:

[0019] φ c =γG c t c Δz

[0020] In the formula, φ c is the broken gradient dispersion, γ is the gyromagnetic ratio, G c is the crushing gradient amplitude, t c is the crushing gradient duration, the crushing gradient is applied in the Z direction, Δz is the voxel size in the Z direction, in the horizontally placed main magnet, the Z direction is defined as the direction pointing to the observer. The X direction is the direction from left to right. The Y direction is the direction from bottom to top.

[0021] In step S5, the amplitude of the spoiler gradient pulse is calculated according to the desired spoiler gradient dephasing:

[0022] φ s =γG s t s Δr

[0023] In the formula, φ s is the spoiler gradient dephasing, γ is the gyromagnetic ratio, G s is the spoiler gradient amplitude, t s is the duration of the spoiler gradient. The spoiler gradient is applied in any one of the X, Y and Z directions. Δr is the voxel size in the selected direction. In the horizontally placed main magnet, the Z direction is defined as the direction pointing to the observer, the Y direction is from bottom to top, and the X direction is from left to right.

[0024] In step S6, the magnetic resonance imaging K-space acquisition may be EPI fast imaging or other spatial encoding methods.

[0025] The present invention also discloses the application of the above REXI sequence in magnetic resonance imaging. The application is the application of magnetic resonance imaging to measure the transmembrane transport of cerebrospinal fluid. Further, the application is the application of magnetic resonance imaging to measure the molecular exchange rate between the short T2 component and the long T2 component in a two-component system. Still further, the application is to measure the water molecule exchange rate of the choroid plexus (short T2 component)-cerebrospinal fluid (long T2 component) or the water molecule cross-barrier exchange rate of the cerebrospinal fluid (long T2 component)-brain parenchyma (short T2 component) exchange interface.

[0026] The present invention also provides a method for collecting and analyzing the above REXI sequence, the method comprising:

[0027] (1) Using a multi-layer multi-echo MSME sequence at different echo times TE eq The magnetic resonance signal S is collected eq ;

[0028] (2) Using the REXI sequence, the filter module TE f Set to a fixed value, at different exchange times t m and echo time TE of different detection modules d Collect magnetic resonance imaging signal S(t m ,TE d );

[0029] (3) Using the magnetic resonance signal S acquired in step (1) eq Fitting the short T2 component fraction under equilibrium state Transverse relaxation time T2 of the short T2 component shortand the transverse relaxation time T2 of the long T2 component long , and the initial signal S 0 ;

[0030] (4) Using the magnetic resonance signal S(t m ,TE d ) and step (3) T2 short and T2 long Fitting different exchange times t m The short T2 component proportion f short (t m );

[0031] (5) Using step (3) and f in step (4) short (t m ), and the apparent water molecule exchange rate k is obtained by fitting;

[0032] (6) Using step (3) The apparent water molecule exchange rate is corrected for k in step (5), and the water molecule efflux rate constant k of the short T2 component is finally obtained: sl .

[0033] The magnetic resonance sequence provided by the present invention adopts relaxation-based exchange weighted imaging: in 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; REXI analysis adopts a double-chamber exchange model to fit the data; specifically, the least squares sum method is used to fit the magnetic resonance signals under different exchange times, and the apparent water molecule exchange rate and the short T2 component water molecule outflow rate constant are obtained by combining the short T2 component proportion fraction parameter.

[0034] Preferably, in steps (1) and (2): the readout scheme of the detection module in the MSME sequence and the REXI sequence can be changed to a planar echo imaging (EPI) acquisition encoding method to speed up the imaging speed; the detection module can be combined with multiple excitation EPI (multi-shot EPI) and multi-band EPI technology (simultaneous multi-layer SMS technology) to simultaneously achieve the requirements of short TE and multi-layer rapid scanning.

[0035] Preferably, the magnetic resonance imaging method further comprises preprocessing (motion correction, etc.) the MSME sequence and REXI sequence images.

[0036] The echo time of the filtering module and the echo time of the detection module are fixed, and only the switching delay time of the switching module is changed.

[0037] Preferably, the filtration module TE in step (2) fParameters are generally set to be more than twice the short T2 in the dual T2 component system.

[0038] Preferably, in step (3), according to the formula

[0039] Further preferably, the T1 of the short T2 component and the long T2 component can be different. short (t m ) is corrected. Preferably, in step (4), according to the formula Fitting, substitute T2 obtained in the previous step short and T2 long , fitting to obtain different exchange times t m The short T2 component proportion f short (t m ), where S(t m ,TE d ) is the REXI detection module at different t m Multi-echo acquisition (TE d ) obtained, the initial signal S 0 (t m ).

[0040] Preferably, in step (5), according to the formula Fitting: The apparent water molecule exchange rate (k) is obtained by fitting using the least squares method. It is the fraction of the instantaneous short T2 component after the fitted filtering module is applied.

[0041] Preferably, in step (6), according to the formula Correction was made for apparent water molecule exchange rates.

[0042] 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 water molecule cross-barrier exchange rate at the cerebrospinal fluid-brain parenchyma exchange interface, and the short T2 component water molecule outflow rate constant is the choroid plexus water molecule outflow rate constant or the brain parenchyma water molecule outflow rate constant.

[0043] In the above method, when used for a magnetic resonance imaging method for measuring the exchange rate between short T2 components and long T2 components in different tissues, the detection module echo time TE of the relaxation exchange imaging REXI sequence can be adjusted as needed. d Exchange time t m and filter module echo time.

[0044] The present invention also provides an application of the above-mentioned acquisition and analysis method in magnetic resonance imaging. The application is the application of magnetic resonance imaging to measure the transmembrane transport of cerebrospinal fluid. Further, the application is the application of magnetic resonance imaging to measure the molecular exchange rate between the short T2 component and the long T2 component in a two-component system. Still further, the application is to measure the water molecule exchange rate of the choroid plexus (short T2 component)-cerebrospinal fluid (long T2 component) or the water molecule cross-barrier exchange rate at the cerebrospinal fluid (long T2 component)-brain parenchyma (short T2 component) exchange interface.

[0045] Compared with the prior art, the present invention has the following excellent effects:

[0046] The REXI sequence and the acquisition and analysis method thereof provided by the present invention are suitable for measuring the water molecule exchange rate magnetic resonance imaging of a T2 two-component system. f Parameters, the existing three-dimensional acquisition of relaxation exchange nuclear magnetic resonance spectrum REXSY is changed to the two-dimensional acquisition of relaxation exchange magnetic resonance imaging REXI, which greatly improves the acquisition speed of water molecule exchange rate magnetic resonance imaging measurement.

[0047] The relaxation exchange magnetic resonance imaging REXI sequence and the acquisition and analysis method thereof provided by the present invention have a spatial imaging function and can provide the spatial distribution of the water molecule exchange rate of the T2 two-component system. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] Figure 1 A schematic diagram of a REXI sequence used in the present invention;

[0049] Figure 2 This is an operation flow chart of the magnetic resonance imaging method for measuring the choroid plexus-cerebrospinal fluid water molecule exchange rate using the REXI sequence in Example 1;

[0050] Figure 3 The REXI images at different exchange times in Example 1;

[0051] Figure 4 is the choroid plexus tissue proportion fraction f fitted in Example 1 short (t m ) About t m The curve of

[0052] Figure 5 is the choroid plexus water molecule outflow rate constant k obtained by fitting the curve and correction in Example 1 sl ;

[0053] Figure 6 This is the structural image of the rat brain in Example 2 and the choroid plexus region of interest (ROI) outlined on the structural image. DETAILED DESCRIPTION

[0054] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be clearly and completely described below in conjunction with the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0055] The REXI sequences used in the present invention are as follows Figure 1 As shown. The sequence includes three modules, namely, filter block, mixing time and detection block. Both the filter block and the detection block are spin echo sequences. Taking the measurement of the exchange rate of water molecules between the choroid plexus (short T2 component) and cerebrospinal fluid (long T2 component) as an example, the role of each module is explained: the filter module is used to filter (suppress) the magnetization vector of the choroid plexus water molecules, and by setting the appropriate filter module echo time, i.e., TE f The value suppresses the choroid plexus tissue signal and avoids a 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, the water molecules in the choroid plexus and the water molecules in the cerebrospinal fluid are exchanged. The filtered (inhibited) water molecules can restore the signal through cross-barrier water exchange. The degree of recovery varies with the exchange time (t m ) increases; the detection module uses multi-echo acquisition to quantify the proportion of exchanged and unexchanged water molecules, and can detect the m Magnetic resonance signal after exchange time; Paired crusher gradient (G c ) can replace the phase cycle to shorten the acquisition time; spoiler gradient (G s ) is used to remove the residual transverse magnetization vector. In order to increase the image signal-to-noise ratio and remove the inflow effect, the pulses in the filtering module are all non-selective pulses; the pulses in the detection module are slice-selective pulses.

[0056] Specifically, the filtering module is composed of one 90° excitation RF pulse (the first 90° excitation RF pulse) and one 180° refocusing RF pulse (the first 180° refocusing RF pulse), and the interval time between the 90° excitation RF pulse (the first 90° excitation RF pulse) of the filtering module and the 180° refocusing RF pulse (the first 180° refocusing RF pulse) of the filtering module is TE f / 2, the interval time between the 180° refocusing RF pulse (the first 180° refocusing RF pulse) of the filtering module and the subsequent 90° excitation RF pulse (the second 90° excitation RF pulse) in the switching module is TE f / 2; the exchange module is composed of one 90° excitation RF pulse (the second 90° excitation RF pulse), and the interval between the 90° excitation RF pulse (the second 90° excitation RF pulse) and the subsequent 90° excitation RF pulse (the third 90° excitation RF pulse) in the detection module is the exchange time (t m ); The detection module is composed of a 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 detection module echo time (TE d ), the interval time 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) in the detection module is TE / 2. After TE / 2, each 180° refocusing RF pulse in the detection module can generate an echo signal for filling the magnetic resonance K-space data and finally reconstructing a magnetic resonance image.

[0057] Then, according to the desired crushing gradient phase dispersion, the crushing gradient pulses in the filter module and the detection module are calculated. The crushing gradient consists of two pulses with the same application direction (Z direction) and duration (t c ) and amplitude (G c ) are composed of the same gradients, where the first crushing gradient is applied before the 90° excitation RF pulse of the exchange module, and the second crushing gradient is applied after the 90° excitation RF pulse of the detection module. c ), the following relationship needs to be satisfied:

[0058] φ c =γG c t c Δz

[0059] Where Δz is the voxel size in the Z direction. In a horizontally placed main magnet, the Z direction is defined as the direction pointing to the observer. The X direction is from left to right. The Y direction is from bottom to top. According to experience, the minimum φ c Usually it is greater than or equal to 4π.

[0060] Then, the spoiler gradient pulses in the exchange module are calculated according to the desired spoiler gradient dephasing. The spoiler gradient can be applied in the X, Y or Z direction alone, or in all three directions at the same time. In this embodiment 1, the spoiler gradient is applied in the Z direction. The amplitude of the spoiler gradient is Gs , duration is t s , in order to produce the desired spoiler gradient dephasing (φ s ), the following relationship needs to be satisfied:

[0061] φ s =γG s t s Δr

[0062] Where Δr is the voxel size in the selected direction, usually set to φ s Greater than or equal to 8π.

[0063] Therefore, the REXI sequence is performed in the following ways:

[0064] S1, applying a first 90° excitation radio frequency pulse, and then applying a first 180° refocusing radio frequency pulse;

[0065] S2, applying a crushing gradient pulse;

[0066] S3, applying a second 90° excitation radio frequency pulse;

[0067] S4, applying spoiler gradient pulses;

[0068] S5, applying a third 90° excitation radio frequency pulse;

[0069] S5, applying a crushing gradient pulse;

[0070] S6. Apply a second 180° refocusing radio frequency pulse and perform magnetic resonance imaging K-space acquisition.

[0071] Example 1

[0072] As a specific example, 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 the cerebrospinal fluid (long T2 component). That is, the REXI sequence provided by the present invention is applied to the brain of WistarKyoto rats for magnetic resonance imaging to measure the water molecule exchange rate between the choroid plexus and the cerebrospinal fluid. The acquisition and analysis flow chart is shown in Figure 2 , specifically including the following steps:

[0073] Step 1: Place the anesthetized rat in a 9.4T magnetic resonance imaging system, and use the center of the lateral ventricle as the scanning center point to perform single-layer image acquisition. In this embodiment, magnetic resonance data of 8 rats were acquired.

[0074] Step 2: Set the MSME sequence and set the resolution to 0.27×0.36mm 2, slice thickness 1.5mm, single-layer acquisition. The number of echoes is 30, and the echo time is 7, 14, 21, ... 203, 210ms. The sequence repetition time (TR) is 2500ms, and the imaging results of the MSME sequence (magnetic resonance signal S eq ).

[0075] Step 3: Set the REXI sequence and the resolution to 0.27×0.36mm 2 , layer thickness 1.5mm, single layer acquisition. The fixed filter module echo time of the filter module should be set to 30ms. The detection module is set to multi-echo detection, the number of echoes is 30, and the echo time is 7, 14, 21, ... 203, 210ms. The exchange module is set to 4 different exchange times (t m ) are 25ms, 100ms, 200ms, and 400ms respectively for multiple measurements. The sequence repetition time (TR) is variable and is 2500ms+t m , obtain the imaging results of REXI sequence (magnetic resonance signal S(t m )).

[0076] In this embodiment, φ c Usually set to 4π, φ s Usually set to 8π.

[0077] Step 4: Using the magnetic resonance signal collected in step 2, according to the formula Fitting the choroid plexus tissue fraction in equilibrium The transverse relaxation time (T2 short ) and the transverse relaxation time of cerebrospinal fluid (T2 long )(and the initial signal S 0 ), where S eq Magnetic resonance signals acquired at different TE.

[0078] Step 5: Using the magnetic resonance signal S(t m ) and step 4 to fit the choroid plexus tissue fraction in equilibrium The transverse relaxation time (T2 short ) and the transverse relaxation time of cerebrospinal fluid (T2 long ), according to the formula Fitting different t m The choroid plexus tissue fraction f short (t m ), where S(t m ,TE d ) is the multi-echo acquisition (TE) of the REXI detection module d) obtained, the initial signal S 0 (t m ).

[0079] Step 6: Use the choroid plexus tissue fraction at equilibrium obtained in step 4 Different from the one obtained in step 5 m The choroid plexus tissue fraction f short (t m ), for the formula The apparent water molecule exchange rate (k) was obtained by fitting using the least squares method. At the same time, the instantaneous choroid plexus tissue fraction after the filtration module was applied was also obtained by fitting.

[0080] Step 7: Use the choroid plexus tissue fraction at equilibrium obtained in step 4 and the apparent water molecule exchange rate (k) obtained in step 6, according to the formula The apparent water molecule exchange rate between the choroid plexus and cerebrospinal fluid was corrected, and the choroid plexus water molecule outflow rate constant (k sl ).

[0081] To demonstrate the effect of this embodiment in measuring the choroid plexus-cerebrospinal fluid water molecule exchange rate, the experimental results of this specific embodiment will be described below in conjunction with the accompanying drawings:

[0082] Take the results of a single-layer image of a single rat as an example. Figure 3 The different exchange times t obtained in step 3 of this specific embodiment are shown m The REXI image below. Figure 3 As shown in the figure, the lateral ventricles are very obvious in the REXI image, and their signals are higher than the surrounding tissue signals, while the lateral ventricles and tissues in the MSME image are difficult to distinguish; this indicates that the filtering module of REXI suppresses the signals of tissues well. Figure 4 The fifth step of this specific embodiment is to fit the REXI signal to obtain different t m The choroid plexus tissue fraction f short (t m ). Observe that f short (t m ) m It increased, indicating that the proportion of choroid plexus tissue was restored within the exchange module. Figure 5 The fitting curve in step 6 and the choroid plexus water efflux rate constant (k) obtained by correction in step 7 are shown. sl ). This shows that the fitting formula in step 6 can better fit different t m The choroid plexus tissue fraction f short (tm ) was fitted, and finally the choroid plexus water molecule outflow rate constant (k sl ).

[0083] In summary, the REXI sequence and magnetic resonance imaging method provided by the present invention (mainly including two-component exponential fitting and exchange rate fitting of transverse relaxation time and component proportion) can be used to measure the steady-state outflow rate of water molecules from the choroid plexus to the cerebrospinal fluid.

[0084] Example 2

[0085] Based on Example 1, as another achievable manner, the following optional steps may be added to achieve more accurate delineation of the region of interest based on the choroid plexus structure image. The optional steps are as follows:

[0086] Step 1: Set the T2 TurboRARE sequence with 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 the structural image of the rat brain.

[0087] Step 2: Outline the choroid plexus tissue region of interest on the high-resolution structural image obtained in step 1, and use a bilinear interpolation algorithm to downsample the region of interest image to the same resolution as the REXI image to obtain the final choroid plexus mask. Figure 6 Shown is a structural image of the rat brain and the choroid plexus region of interest (ROI) outlined on the structural image.

[0088] Step 3: Using the choroid plexus mask obtained in step 2, average the MSME or REXI image signal values ​​of all pixels in the mask to perform the following Figure 2 Parameters analyzed as shown.

[0089] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in 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 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 fragmentation gradient pulses in the filtering module and the detection module; and applying spoiler gradient pulses in the exchange module.

2. The REXI sequence of relaxation exchange magnetic resonance imaging according to claim 1, characterized in that: The execution method of the REXI sequence includes: S1, applying a first 90° excitation radio frequency pulse, and then applying a first 180° refocusing radio frequency pulse; S2, applying a crushing gradient pulse; S3, applying a second 90° excitation radio frequency pulse; S4, applying spoiler gradient pulses; S5, applying a third 90° excitation radio frequency pulse; S5, applying a crushing gradient pulse; S6, applying a second 180° refocusing radio frequency pulse and performing magnetic resonance imaging K-space acquisition; The interval between the first 90° excitation RF pulse and the second 90° excitation RF pulse is the filter module echo time TE f The intervals between the first 90° excitation RF pulse and the second 90° excitation RF pulse and the first 180° refocusing RF pulse are all 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 time 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 REXI sequence of relaxation exchange magnetic resonance imaging according to claim 2, characterized in that: In the steps S2 and S4, the amplitude of the crushing gradient pulse is calculated according to the desired crushing gradient dephasing: f c =γG c t c Δz In the formula, φ c is the broken gradient dispersion, γ is the gyromagnetic ratio, G c is the crushing gradient amplitude, t c is the crushing gradient duration, the crushing gradient is applied in the Z direction, Δz is the voxel size in the Z direction, and in the horizontally placed main magnet, the Z direction is defined as the direction pointing to the observer.

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

5. A method for collecting and analyzing a REXI sequence of relaxation exchange magnetic resonance imaging, characterized in that: The collection and analysis method comprises: (1) Using a multi-layer multi-echo MSME sequence at different echo times TE eq The magnetic resonance signal S is collected eq ; (2) Using the REXI sequence of any one of claims 1 to 4, the filter module TE f Set to a fixed value, at different exchange times t m and echo time TE of different detection modules d Collect the magnetic resonance signal S(t m ,TE d ); (3) Using the magnetic resonance signal S acquired in step (1) eq Fitting the short T2 component fraction under equilibrium state Transverse relaxation time T2 of the short T2 component short and the transverse relaxation time T2 of the long T2 component long , and the initial signal S0; (4) Using the magnetic resonance signal S(t m ,TE d ) and step (3) T2 short and T2 long Fitting different exchange times t m The short T2 component proportion f short (t m ); (5) Using step (3) and f in step (4) short (t m ), and the apparent water molecule exchange rate k is obtained by fitting; (6) Using step (3) The apparent water molecule exchange rate is corrected for k in step (5), and the water molecule efflux rate constant k of the short T2 component is finally obtained: sl .

6. The method for collecting and analyzing the REXI sequence of relaxation exchange magnetic resonance imaging according to claim 5, characterized in that: In step (3), according to the formula Fitting.

7. The method for collecting and analyzing the REXI sequence of relaxation exchange magnetic resonance imaging according to claim 5, characterized in that: In step (4), according to the formula Fitting; At the same time, fitting obtains the initial signal S0(t m ).

8. The method for collecting and analyzing the REXI sequence of relaxation exchange magnetic resonance imaging according to claim 5, characterized in that: In step (5), according to the formula Fitting; at the same time, fitting obtains the instantaneous short T2 component after the filtering module is applied 9. The method for collecting and analyzing the REXI sequence of relaxation exchange magnetic resonance imaging according to claim 5, characterized in that: In step (6), according to the formula Correction was made for apparent water molecule exchange rates.

10. The method for collecting and analyzing REXI sequence of relaxation exchange magnetic resonance imaging 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 water molecule cross-barrier exchange rate at the cerebrospinal fluid-brain parenchyma exchange interface, and the short T2 component water molecule outflow rate constant is the choroid plexus water molecule outflow rate constant or the brain parenchyma water molecule outflow rate constant.

11. Use of the REXI sequence of any one of claims 1 to 4 and the acquisition and analysis method of any one of claims 5 to 10 in measuring transmembrane transport of cerebrospinal fluid using magnetic resonance imaging.

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

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

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

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