Blood brain barrier water extraction rate imaging method based on artery marking and speed selection

Abstract

The invention discloses a blood brain barrier water extraction rate imaging method and system based on artery marking and speed selection. By marking spinning of water molecules in artery blood and selectively detecting signals of residual marked blood which does not enter brain tissues in vein blood vessels, quantitative evaluation of blood-brain barrier water permeability is realized. According to the method, the neck artery blood flow is magnetized and overturned by adopting pseudo-continuous artery spin labeling, a speed selection module based on Fourier transform is applied in an acquisition stage to eliminate interference of brain tissue signals, pure vein labeling signals are obtained, and rapid and accurate measurement of water extraction fraction and permeability-surface area volume is realized. In addition, the signal-to-noise ratio and robustness are effectively improved by adopting dual suppression pulses of background tissues and blood. The method does not need an exogenous contrast agent, is non-invasive, short in scanning time and accurate and stable in measurement result, and has important clinical application value for early diagnosis of brain diseases and assessment of pathological changes of the blood brain barrier.

Description

Technical Field

[0001] The present application relates to the field of magnetic resonance technology, and in particular to an imaging method for rapid blood-brain barrier measurement. Background Art

[0002] Magnetic resonance imaging of the blood-brain barrier (BBB) ​​is an important MRI technique. Non-invasive measurement of water extraction rate and blood-brain barrier permeability (PS) calculated from water extraction rate are crucial in many brain diseases. Currently, the mainstream method for clinical assessment of BBB permeability is dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). This technique relies on the injection of gadolinium-based contrast agents and infers BBB integrity by measuring their leakage from blood vessels into brain tissue. However, this method has many limitations: (1) it requires exogenous contrast agents and is not suitable for patients with renal insufficiency; (2) it has low sensitivity to slight permeability changes, and the signal is only visible when the BBB is significantly damaged; (3) the contrast agent may remain in the brain, posing a potential toxicity risk; (4) it has poor acceptability during repeated scans and is not suitable for long-term follow-up. To overcome these limitations, noninvasive imaging methods based on arterial spin labeling (ASL) have emerged in recent years. In particular, diffusion-weighted ASL (DP-ASL), which incorporates a diffusion-sensitive gradient, can be used to quantify the exchange rate of water molecules across the BBB (e.g., water exchange rate kw and surface area product PSw), enabling contrast-free permeability assessment. These methods use blood water as endogenous tracers and separate intravascular and intratissue signals through different diffusion weights and post-labeling delay (PLD) imaging. However, existing DP-ASL technology still faces the following challenges: high sensitivity to subject motion and low signal-to-noise ratio, which affect measurement accuracy; high dependence on imaging parameters, which can easily lead to miscalculation due to improper parameter selection; limited ability to resolve small blood flow delays or heterogeneous microcirculatory structures; mostly static modeling, which makes it difficult to fully capture the dynamic transport process of blood from capillaries to tissues; long scanning times and limited resolution, which restrict its widespread clinical application. WEPCAST ​​(Water Extraction with Phase-Contrast Arterial Spin Tagging) is a non-contrast magnetic resonance imaging technique based on arterial spin labeling that can noninvasively and rapidly assess blood-brain barrier water permeability. It offers advantages such as high reproducibility and sensitivity to early lesions, making it particularly suitable for longitudinal follow-up and large-sample studies. However, this method requires long scan times and primarily provides information on average permeability across the entire brain. Its spatial resolution is limited, and its ability to identify focal lesions is poor. Therefore, a non-invasive, contrast-agent-free, highly sensitive, and robust technique for assessing blood-brain barrier function is urgently needed. Summary of the Invention

[0003] To overcome the shortcomings of the existing technology, the present invention proposes a non-contrast agent blood-brain barrier permeability measurement method based on velocity selection, called the blood-brain barrier water extraction rate imaging method based on arterial labeling and velocity selection, to achieve the measurement of water extraction rate of large and small veins and reduce acquisition time.

[0004] In order to achieve the above object, the present invention adopts the following technical solutions:

[0005] In a first aspect, the present invention provides a method for imaging water extraction rate of the blood-brain barrier based on arterial labeling and speed selection, comprising the following steps:

[0006] S1: Applying an MRI sequence combining arterial spin labeling and velocity selection to the subject to be examined, alternating between labeling and control periods for signal acquisition; the MRI sequence employs pseudo-continuous arterial spin labeling (pCASL) technology to magnetize the carotid artery blood flow, and during a post-labeling delay period, a velocity selection module is introduced after the background suppression module to set the flowing blood spins within the target velocity range to a passband and the static tissue spins to a saturation band, thereby selectively extracting the arterial labeled blood signal in the vein and eliminating interference from brain tissue signals. Finally, the MRI signal is read out after the post-labeling delay period.

[0007] S2: Calculate the magnetic resonance signal difference based on the collected magnetic resonance signals during the labeling period and the control period. Then, determine the water extraction fraction (E) of water molecules in arterial blood by brain tissue based on the magnetic resonance signal difference, and calculate the permeability-surface area product (PS).

[0008] As a preferred embodiment of the first aspect, the speed selection module synchronously applies a speed selective saturation pulse sequence and a gradient pulse sequence based on Fourier transform;

[0009] The velocity-selective saturation pulse sequence includes nine 10° excitation pulses and a pair of 180° refocusing radio frequency pulses is inserted between all two adjacent 10° excitation pulses. Both the 10° excitation pulse and the 180° refocusing radio frequency pulse are hard pulses, and all 16 180° refocusing radio frequency pulses adopt an MLEV-16 phase cycle scheme, with phases of 0°-0°-180°-180°-180°-0°-0°-180°-180°-0°-0°-180°-180°-0°. After the last 10° excitation pulse is applied, a destructive gradient for suppressing residual transverse magnetization is applied, and finally a recovery time is waited to restore all magnetization to the longitudinal direction.

[0010] In the gradient pulse sequence, it is necessary to apply triangular gradient pulses with opposite polarities along a specified direction before and after each 180° refocusing radio frequency pulse.

[0011] As a preferred embodiment of the first aspect above, in the velocity selection module, the amplitude and duration of the triangular gradient pulse are pre-adjusted to adjust the cutoff velocity (Vc) of the velocity selection saturation band within the range of 2-30 cm / s. With the cutoff velocity as the boundary, the flowing blood spins with a velocity higher than the cutoff velocity are placed in the pass-band, while the static tissue spins with a velocity lower than the cutoff velocity are placed in the saturation band, thereby achieving the retention of the flowing spin signal and the suppression of the static background.

[0012] As a preferred embodiment of the first aspect, the magnetic resonance sequence includes a pre-saturation module, a labeling / control module, a post-labeling delay module, and a readout module;

[0013] In the pre-saturation module, spatially selective saturation pulses are applied to reduce static tissue and unlabeled blood signals in the scanning area;

[0014] In the labeling / control module, corresponding pulse trains and gradients are applied during the labeling and control periods, respectively, according to the pseudo-continuous arterial spin labeling (pCASL) technique, so that the magnetization of the arterial blood flowing into the brain is reversed during the labeling period to achieve the labeling effect, but the magnetization of the arterial blood flowing into the brain is not reversed during the control period;

[0015] The post-labeling delay module includes a background suppression module and a speed selection module; the background suppression module is first executed to reduce the signal intensity of background tissue and unlabeled blood by applying non-selective inversion pulses that suppress brain tissue signals and blood signals; and the speed selection module is then executed to adjust the cutoff speed of the saturation band;

[0016] In the readout module, single-shot echo planar imaging (EPI) is used to collect magnetic resonance signals of the target area in the brain;

[0017] Preferably, the target area is the superior sagittal sinus (SSS) area.

[0018] Preferably, in the magnetic resonance sequence, the labeling duration is set to 2000-4000 ms, and the post-labeling delay (PLD) is set to 1500 ms-5000 ms.

[0019] Preferably, in the labeling / control module, during the labeling period, a pulse chain consisting of continuous short radio frequency pulses and gradient pulses are applied to reversely label the spins of water molecules in the arterial blood flowing through the labeling plane, wherein the duration of the short radio frequency pulses is 0.3 to 1 millisecond, the time interval between adjacent short radio frequency pulses is 0.5 to 1.5 milliseconds, and the amplitude of the gradient pulses is 5 to 20 mT / m; during the control period, no pulse chain is applied and only the same gradient pulses as those during the labeling period are applied.

[0020] As a preferred embodiment of the first aspect, the water extraction fraction (E) of water molecules in arterial blood by brain tissue is determined based on the magnetic resonance signal difference and is calculated using the following model:

[0021]

[0022] Where: M0 is the equilibrium magnetization of blood, T 1,blood is the longitudinal relaxation time of blood, δ v is the arrival time of the spins to the target area, α is the labeling efficiency, c(t) is the arterial input function with time t as the independent variable, and satisfies when δ v <t<δ v c(t) = 1 when +τ, otherwise 0, where τ is the marking duration.

[0023] As a preferred embodiment of the first aspect, the permeability-surface product (PS) is calculated based on the water extraction fraction (E) using the Renkin-Crone model, and the calculation method is:

[0024] PS=-f·ln(1-E)

[0025] Where: f is the cerebral blood flow (CBF) of the subject to be tested.

[0026] In a second aspect, the present invention provides a blood-brain barrier water extraction rate imaging system based on arterial labeling and speed selection, comprising:

[0027] a data acquisition module, configured to apply a magnetic resonance sequence to the subject to be examined and alternately acquire signals during a labeling period (Label) and a control period (Control); the magnetic resonance sequence employing pseudo-continuous arterial spin labeling (pCASL) technology to magnetize the carotid artery blood flow, and introducing a velocity selection module after the background suppression module during a post-labeling delay period to set the flowing blood spins within a target velocity range to a pass-band and static tissue spins to a saturation band, thereby selectively extracting the arterial labeled blood signal in the vein and eliminating interference from brain tissue signals; and finally, reading the magnetic resonance signal after the post-labeling delay period.

[0028] The calculation and processing module is used to calculate the magnetic resonance signal difference based on the collected labeling period magnetic resonance signals and the control period magnetic resonance signals, and then determine the water extraction fraction (E) of water molecules in arterial blood by brain tissue based on the magnetic resonance signal difference, and calculate the permeability-surface area product (PS).

[0029] In a third aspect, the present invention provides a computer program product comprising a computer program / instruction, which, when executed by a processor, can implement the blood-brain barrier water extraction rate imaging method based on arterial marking and speed selection as described in any one of the first aspects above.

[0030] In a fourth aspect, the present invention provides a computer-readable storage medium having a computer program stored thereon. When the computer program is executed by a processor, the blood-brain barrier water extraction rate imaging method based on arterial marking and speed selection as described in any one of the first aspects above can be implemented.

[0031] In a fifth aspect, the present invention provides a computer electronic device comprising a memory and a processor;

[0032] The memory is used to store computer programs;

[0033] The processor is configured to implement the blood-brain barrier water extraction rate imaging method based on arterial marking and speed selection as described in any one of the first aspects above when executing the computer program.

[0034] Compared with the prior art, the present invention has the following beneficial effects:

[0035] (1) The WEFAST magnetic resonance imaging method provided by the present invention does not require exogenous contrast agents, completely avoiding the risks of nephrogenic systemic fibrosis (NSF), gadolinium deposition, and potential neurotoxicity that may be caused by gadolinium-based contrast agents used in traditional enhanced MRI, significantly improving the safety of clinical application.

[0036] (2) The present invention combines a specific velocity-selective magnetization preparation pulse sequence design with pseudo-continuous arterial spin labeling (pCASL), thereby achieving highly sensitive and highly selective detection of blood flow signals within a specific velocity range, effectively suppressing interference from static tissue signals and blood flow signals in non-target velocity ranges, significantly improving the signal-to-noise ratio and vascular display clarity of magnetic resonance angiography, improving the imaging effect of small blood vessels and slow blood flow, and effectively enhancing the robustness to magnetic field inhomogeneity, significantly improving the accuracy and reliability of contrast-free magnetic resonance angiography.

[0037] (3) The dual suppression pulse scheme of background tissue and blood adopted in the present invention can simultaneously suppress the brain tissue background signal and the non-labeled blood signal, significantly improving the contrast between the target signal and the background noise, greatly improving the signal-to-noise ratio (SNR) of the image and the stability of the data, thereby improving the robustness of the measurement results. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 Schematic diagram of the steps for the method to image water extraction rate from the blood-brain barrier based on arterial labeling and velocity selection;

[0039] Figure 2 It is the WEFAST sequence diagram;

[0040] Figure 3 Schematic diagram of the speed selection module in the WEFAST sequence;

[0041] Figure 4 Typical sagittal and coronal scanning positions for MRI using the WEFAST sequence, with the red arrow pointing to the superior sagittal sinus region;

[0042] Figure 5 A comparison diagram of the signal acquisition and calculation processes between the WEFAST sequence and the WEPCAST ​​sequence in the prior art;

[0043] Figure 6 Schematic diagram of the modular composition of the blood-brain barrier water extraction rate imaging system based on arterial labeling and speed selection;

[0044] Figure 7 It is a schematic diagram of the structure of computer electronic equipment;

[0045] Figure 8 These are some of the experimental results in the examples of the present invention, where (A) is a representative illustration of the WEFAST control image, labeled image, and difference image from one subject, compared with the original WEPCAST ​​image; (B) is a scatter plot of the water extraction rate (E) and the blood-brain barrier permeable surface area product (PS) obtained by WEFAST and original WEPCAST ​​magnetic resonance imaging; (C) is a Bland-Altman analysis of E and PS obtained by WEFAST and original WEPCAST ​​magnetic resonance imaging in 8 subjects.

[0046] Figure 9Figure 2 shows another set of experimental results in the examples of the present invention, where (A) shows the WEFAST control image, labeled image, and difference image of a subject undergoing two consecutive rounds of experiments, and (B) shows the comparison of the coefficient of variation (CoV) between intersession and intrasession of the water extractable fraction (E) and the product of the permeable surface area of ​​the blood-brain barrier (PS) estimated by the WEFAST and original WEPCAST ​​methods. DETAILED DESCRIPTION

[0047] In order to make the above-mentioned objects, features and advantages of the present invention more clearly understood, the specific embodiments of the present invention are described in detail below with reference to the accompanying drawings. In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention can be implemented in many other ways than those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below. The technical features in the various embodiments of the present invention can be combined accordingly without conflicting with each other.

[0048] In the description of the present invention, it should be understood that the terms "first" and "second" are only used for distinguishing description purposes and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features.

[0049] See also Figure 1 The figure shows the process flow of the present invention's blood-brain barrier water extraction rate imaging method based on arterial labeling and velocity selection, which includes steps S1 and S2. This method utilizes a velocity selection module combined with pseudo-continuous arterial spin labeling (pCASL) technology to quantify water extraction rates in large and small cerebral veins in just three minutes. The specific implementation steps of this method are described in detail below.

[0050] S1: Applying an MRI sequence combining arterial spin labeling and speed selection to the subject to be examined, and alternately collecting signals during the labeling period (Label) and the control period (Control), to obtain the labeling period MRI signal and the control period MRI signal, respectively.

[0051] In the magnetic resonance sequence combining arterial spin labeling and velocity selection adopted by the present invention, pseudo-continuous arterial spin labeling (pCASL) technology is used to perform magnetization reversal on the carotid artery blood flow, and a velocity selection module is introduced after the background suppression module during the post-labeling delay period to set the flowing blood spins in the target velocity range to the pass-band, and the static tissue spins to the saturation band, thereby selectively extracting the arterial labeled blood signals in the veins and eliminating the interference of brain tissue signals, and finally reading the magnetic resonance signals after the post-labeling delay period. For ease of description, the magnetic resonance sequence adopted by the present invention is referred to as the WEFAST (Water-Extraction-with-Fourier-transform-velocity-selective-Arterial-Spin-Tagging) sequence, and the sequence as a whole is as follows: Figure 2 As shown in Figure 2, the core of the pCASL system is the introduction of a velocity selective module based on the pCASL sequence. This velocity selective module synchronously applies a Fourier transform-based velocity selective saturation pulse train (FT-VS Pulse Train) and a gradient pulse train. The following describes the specific design of the pulse sequence in the velocity selective module.

[0052] See also Figure 3 As shown, RF and GRO show the pulse trains of the Fourier transform-based velocity selective saturation pulse sequence and gradient pulse sequence, respectively.

[0053] from Figure 3 It can be seen that the velocity-selective saturation pulse sequence in the velocity selection module includes nine 10° excitation pulses with a pair of 180° refocusing RF pulses inserted between each adjacent 10° excitation pulse, resulting in a total of 16 180° refocusing RF pulses. The nine 10° excitation pulses and the 16 180° refocusing RF pulses are all hard pulses. Furthermore, all 16 180° refocusing RF pulses use an MLEV-16 phase cycle scheme, with phases sequentially following the order of 0°-0°-180°-180°-180°-0°-0°-180°-180°-180°-0°-0°-180°-180°-0°. This MLEV-16 phase cycle scheme can improve the module's immunity to magnetic field (B0) and RF field (B1) inhomogeneities. After the final 10° excitation pulse is applied, a destruction gradient is applied to suppress any residual transverse magnetization, and finally a recovery time is allowed to ensure that all magnetization is longitudinal at the beginning of the next repetition time.

[0054] In the velocity-selective saturation pulse sequence, two adjacent 10° excitation pulses and two 180° refocusing RF pulses between them constitute a velocity encoding step. In a gradient pulse sequence, a gradient pulse is required for each velocity encoding step to offset the eddy current effect.

[0055] Continue to see Figure 3 It can be seen that in the gradient pulse sequence in the velocity selection module, it is necessary to apply triangular gradient pulses with opposite polarities along the specified direction before and after each RF pulse of a pair of 180° refocusing RF pulses in each velocity encoding step. It should be noted that Figure 3 From a timing perspective, triangular gradient pulses are paired before and after each 180° refocusing RF pulse. The 180° refocusing RF pulse follows the previous triangular gradient pulse, and the next triangular gradient pulse follows the 180° refocusing RF pulse. The two triangular gradient pulses before and after each 180° refocusing RF pulse have the same amplitude and duration but opposite polarity. These triangular gradient pulses are applied along a specific direction (in this embodiment, the direction can be selected along the slice) to achieve velocity encoding. The triangular shape of the gradient waveform effectively offsets eddy current effects.

[0056] Based on the above Figure 3 The speed selection module shown in the figure is further described below. Figure 2 As shown in FIG, the WEFAST sequence includes a pre-saturation module (Pre-saturation), a label / control module (Label / Control), a post-labeling delay (PLD) module, and a readout module. The specific form of each module is introduced below.

[0057] In the above-mentioned pre-saturation module, spatially selective saturation pulses are applied to reduce the static tissue (such as fat or background tissue) and unlabeled blood signals in the scanning area.

[0058] In the labeling / control module, corresponding pulse trains (if any) and gradients are applied during the labeling and control periods, respectively, in accordance with pseudo-continuous arterial spin labeling (pCASL) technology. This results in magnetization reversal of arterial blood flowing into the brain during the labeling period, while magnetization reversal is not performed during the control period. Blood flow labeling is primarily achieved in the labeling / control module by applying radiofrequency pulse trains and gradients. Specifically, during the labeling period, a pulse train consisting of continuous short radiofrequency pulses and gradient pulses are applied to reverse the spins of water molecules in arterial blood flowing through the labeling plane. The specific parameters of the pulse train and gradient can be set based on the actual test subject and relevant guidelines and experience with pCASL technology. In an embodiment of the present invention, the duration of the short radiofrequency pulses is controlled to be 0.3 to 1 millisecond, the time interval between adjacent short radiofrequency pulses is controlled to be 0.5 to 1.5 milliseconds, and the amplitude of the gradient pulses is controlled to be 5 to 20 mT / m. During the control period, no pulse train is applied; only the same gradient pulses as used during the labeling period are applied.

[0059] The post-labeling delay module includes a background suppression module and a velocity selective module. These two submodules are executed sequentially: first, the background suppression module is executed to reduce the signal intensity of background tissue and unlabeled blood by applying non-selective inversion pulses that suppress brain tissue signals and blood signals; then, the velocity selective module is executed to adjust the cutoff velocity of the saturation band. The background suppression module includes two types of pulses with different suppression targets: multiple non-selective inversion pulses for suppressing brain tissue signals and multiple non-selective inversion pulses for suppressing blood signals. By designing the timing of these two types of suppression pulses, the signals of background tissue and unlabeled blood can be reduced to less than 5% of the equilibrium magnetization intensity.

[0060] In the above-mentioned readout module, single-shot echo planar imaging (EPI) is used to acquire magnetic resonance signals of the target area in the brain. It should be noted that the target area in the present invention needs to be set according to actual needs, and different target areas may require different optimization sequence parameters.

[0061] In an embodiment of the present invention, the target area may be set to the superior sagittal sinus (SSS) area. Figure 4The following figure shows typical sagittal and coronal scanning positions for MRI using the WEFAST sequence. The red arrow indicates the superior sagittal sinus region. Therefore, during data acquisition, the EPI module can be used to rapidly acquire arterial blood signals from the superior sagittal sinus region to facilitate subsequent measurement of the water extraction fraction (E). For this region, the labeling duration can be set to 2000–4000 ms, and the post-labeling delay (PLD) can be set to 1500–5000 ms.

[0062] Therefore, based on the above Figure 2 The specific execution process of the WEFAST sequence shown in the figure for magnetic resonance detection is as follows:

[0063] 1) A marking plane is set upstream of the subject's cerebral artery. A pre-saturation module is first applied to reduce the static tissue and unmarked blood signals within the scan area using spatially selective saturation pulses.

[0064] 2) Subsequently, according to the conventional practice of the pCASL sequence, a series of continuous short radiofrequency pulses and synchronized gradient pulses are applied in the labeling / control module to continuously invert the spins of water molecules in the arterial blood flowing through the labeling plane. The continuous radiofrequency pulse duration is 0.3 to 1 millisecond, the time interval between adjacent radiofrequency pulses is 0.5 to 1.5 milliseconds, and the gradient pulse amplitude is 5 to 20 mT / m, ensuring that the arterial blood spin labeling efficiency reaches greater than 80%.

[0065] 3) After arterial spin labeling is completed, the post-labeling delay (PLD) module is executed, with a PLD range of 2500ms to 5000ms. During the PLD process, the background suppression module is first applied, using multiple non-selective inversion pulses to reduce the signal from static tissue and unlabeled flowing blood within the scan area to less than 5% of the equilibrium magnetization. Furthermore, a velocity selection module is added to the post-labeling delay (PLD) of the pseudo-continuous arterial spin labeling (pCASL) module. This module consists of nine 10° excitation pulses, each separated by a pair of 180° refocusing RF pulses. These RF pulses are hard pulses. The refocusing pulses use an MLEV-16 phase cycle scheme (0°-0°-180°-180°-180°-0°-180°-180°-0°-0°-180°-180°-0°-180°-0°) to improve the module's immunity to magnetic field (B0) and RF field (B1) inhomogeneities. A destruction gradient is then added to suppress any residual transverse magnetization, followed by a recovery time to ensure that all magnetization is longitudinal at the beginning of the next repetition time. Within each velocity encoding step, the pair of refocusing RF pulses is located between a set of gradient pulses of alternating polarity. These gradients are applied along a specific direction (e.g., the slice selection direction) to achieve velocity encoding, and the gradient waveforms are designed to be triangular in shape to more effectively counteract the effects of eddy currents.

[0066] 4) After waiting for PLD, the readout module is executed to realize data acquisition. The single-shot echo planar imaging (EPI) module is used to quickly acquire the arterial marker blood signal in the posterior superior sagittal sinus region to complete the subsequent measurement of the water molecule extraction fraction (E).

[0067] It should be noted that, in accordance with conventional pCASL technology practices, the labeling / control module can only execute one of the labeling phase or the control phase at a given moment. The corresponding pulses for the labeling and control phases are applied alternately, not simultaneously. After the presaturation module completes and the RF pulse train and gradient pulses for the labeling phase are applied, the PLD module and readout module are executed to obtain the MRI signal for the labeling phase. Similarly, after the presaturation module completes and the gradient pulses for the control phase (the RF pulse train is not required in this case), the PLD module and readout module are executed to obtain the MRI signal for the control phase.

[0068] It should also be noted that, among the above-mentioned pre-saturation module, labeling / control module, post-labeling delay module and readout module, except for the speed selection module, the specific parameters and details of the remaining modules can be set according to the general practice of the pCASL sequence.

[0069] In addition, the specific parameters in the aforementioned velocity selection module need to be reasonably optimized, as they directly determine the cutoff velocity (Vc) of the saturation band. The main parameters in the velocity selection module that affect the cutoff velocity (Vc) are the amplitude and duration of the triangular gradient pulse in the GRO gradient pulse sequence. Therefore, in the present invention, the cutoff velocity of the saturation band needs to be determined based on actual detection requirements, and the amplitude and duration of the triangular gradient pulse are then pre-optimized to meet this cutoff velocity. In an embodiment of the present invention, the cutoff velocity (Vc) is generally controlled to be in the range of 2-30 cm / s. The cutoff velocity of the velocity selection saturation band can be adjusted within this range. Using the cutoff velocity as a boundary, flowing blood spins with a velocity above the cutoff velocity are placed in the passband, while static tissue spins below the cutoff velocity are placed in the saturation band, thereby achieving the preservation of the flowing spin signal and the suppression of the static background. In an embodiment of the present invention, taking the commonly used cutoff velocity as an example, setting Vc = 2 cm / s, the amplitude of the triangular gradient pulse is optimized to 20 mt / m, and the duration is optimized to 0.75 ms. Furthermore, the parameters of the 10° excitation pulse and 180° refocusing RF pulse in the RF pulse train also affect B0 and B1 field inhomogeneities and therefore require optimization. In an embodiment of the present invention, the amplitude of the 10° excitation pulse is optimized to 163.9 volts and the duration is optimized to 0.04 ms, while the amplitude of the 180° refocusing RF pulse is optimized to 196.997 volts and the duration is optimized to 1.2 ms. Of course, these optimized parameters represent only a set of preferred parameters in this embodiment and do not limit the present invention.

[0070] After obtaining the labeled and control magnetic resonance signals of the subject to be tested by executing the aforementioned WEFAST sequence, the subsequent step S2 can be executed to process and calculate the signal data to obtain two blood-brain barrier-related index parameters: the water extraction fraction (E) and the permeability-surface product (PS). It should be noted that the labeled and control magnetic resonance signals of the subject to be tested are actually in the form of images, which record the labeled and control magnetic resonance signals of each voxel in the target area. Since the signal processing method for each voxel is the same, the subsequent step S2 describes the specific processing and calculation process using voxels as units.

[0071] S2: Calculate the magnetic resonance signal difference based on the collected magnetic resonance signals during the labeling period and the control period. Then, determine the water extraction fraction (E) of water molecules in arterial blood by brain tissue based on the magnetic resonance signal difference, and calculate the permeability-surface area product (PS).

[0072] In step S2, the water extraction fraction (E) is determined based on the labeled and control MRI signals acquired after PLD (PLD) in step S1. The Renkin-Crone model is then used to fit the data to obtain quantitative blood-brain barrier water permeability parameters. During the model fitting process, the blood-brain barrier water permeability (PS) is the value to be fitted, while the other parameters are known. The specific calculation process for E and PS is described in detail below.

[0073] For the water extraction fraction E, the signal difference ΔM can be obtained by subtracting the magnetic resonance signal of the control period from the magnetic resonance signal of the superior sagittal sinus (SSS) during the labeling period. a (t), then according to ΔM a The water extraction rate (E) is calculated based on the signal model of (t) and water extraction rate (E). The specific signal model is as follows:

[0074]

[0075] Where: M0 is the equilibrium magnetization of blood (MR Signal / 100ml blood), T 1,blood is the longitudinal relaxation time of blood (T1), δ v is the arrival time of the spin to the superior sagittal sinus (SSS) (Bolus ArrivalTime), α is the labeling efficiency, c(t) is the arterial input function with time t as the independent variable, and satisfies when δ v <t<δ v c(t) = 1 if +τ and 0 otherwise, where τ is the labeling duration. Note that in this signal model, the reversed spins always relax at the T1 of blood. Therefore, the T1 of tissue does not appear in the formula.

[0076] In an embodiment of the present invention, after obtaining the water extraction rate (E), the permeability-surface area product (PS) can be calculated according to the water extraction fraction (E) using the Renkin-Crone model. The Renkin-Crone model formula is as follows:

[0077] PS=-f·ln(1-E)

[0078] Where: PS is the permeability-surface product of the superior sagittal sinus (SSS), representing the blood-brain barrier permeability, with the unit of mL / 100 g / min; E is the water extraction fraction (Extraction Fraction), which is a dimensionless parameter; f is the cerebral blood flow (CBF), with the unit of mL / 100 g / min, which can be measured separately by existing technical methods.

[0079] It can be seen that the signal acquisition and calculation process between the WEFAST sequence of the present invention and the WEPCAST ​​(Water Extraction with Phase-Contrast Arterial Spin Tagging) sequence in the prior art are compared. Figure 5 As shown in Figure 2, the WEFAST sequence eliminates the phase-contrast bipolar gradients required in the original WEPCAST ​​by introducing a velocity selection module. Compared to the original WEPCAST ​​sequence, which requires four acquisitions (ControlPC+ and ControlPC-, LabelPC+ and LabelPC-) and double subtraction, WEFAST requires only a single subtraction of the control image (VS Control) and the labeled image (VS Label), while still selectively measuring venous ASL signals. This significantly shortens the time required to quantify the water extraction rate of large and small cerebral veins to under three minutes.

[0080] It should be noted that the method steps shown in S1 to S2 above can essentially be implemented in the form of computer programs or software function modules.

[0081] Therefore, based on the same inventive concept, Figure 6 As shown, the present invention also provides a blood-brain barrier water extraction rate imaging system based on arterial markers and speed selection corresponding to the blood-brain barrier water extraction rate imaging method based on arterial markers and speed selection provided in the above embodiment, comprising:

[0082] a data acquisition module, configured to apply a magnetic resonance sequence to the subject to be examined and alternately acquire signals during a labeling period (Label) and a control period (Control); the magnetic resonance sequence employing pseudo-continuous arterial spin labeling (pCASL) technology to magnetize the carotid artery blood flow, and introducing a velocity selection module after the background suppression module during a post-labeling delay period to set the flowing blood spins within a target velocity range to a pass-band and static tissue spins to a saturation band, thereby selectively extracting the arterial labeled blood signal in the vein and eliminating interference from brain tissue signals; and finally, reading the magnetic resonance signal after the post-labeling delay period.

[0083] The calculation and processing module is used to calculate the magnetic resonance signal difference based on the collected labeling period magnetic resonance signals and the control period magnetic resonance signals, and then determine the water extraction fraction (E) of water molecules in arterial blood by brain tissue based on the magnetic resonance signal difference, and calculate the permeability-surface area product (PS).

[0084] In addition, based on the same inventive concept, Figure 7 As shown, the present invention also provides a computer electronic device corresponding to the blood-brain barrier water extraction rate imaging method based on arterial marking and speed selection provided in the above embodiment, which includes a memory and a processor;

[0085] The memory is used to store computer programs;

[0086] The processor is configured to implement the blood-brain barrier water extraction rate imaging method based on arterial marking and speed selection as described above when executing the computer program;

[0087] Furthermore, the logic instructions in the aforementioned memory can be implemented as software functional units and, when sold or used as independent products, can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of the present invention, or the portion that contributes to the prior art, or a portion of the technical solution, can be embodied in the form of a software product. This computer software product is stored in a storage medium and includes several instructions for causing a computer device (which can be a personal computer, server, or network device, etc.) to execute all or part of the steps of the method described in each embodiment of the present invention.

[0088] Therefore, based on the same inventive concept, the present invention provides a computer-readable storage medium corresponding to a blood-brain barrier water extraction rate imaging method based on arterial markers and speed selection, wherein the storage medium stores a computer program. When the computer program is executed by a processor, the blood-brain barrier water extraction rate imaging method based on arterial markers and speed selection as described above can be implemented.

[0089] Therefore, based on the same inventive concept, the present invention provides a computer program product, including a computer program / instruction, which, when executed by a processor, can implement the blood-brain barrier water extraction rate imaging method based on arterial marking and speed selection as described above.

[0090] Specifically, in the computer-readable storage medium of the above three embodiments, the stored computer program is executed by the processor to perform the above steps S1 to S2.

[0091] It is understood that the storage medium may include random access memory (RAM) or non-volatile memory (NVM), such as at least one disk storage device. Furthermore, the storage medium may be any medium capable of storing program code, such as a USB flash drive, a mobile hard drive, a magnetic disk, or an optical disk.

[0092] It is understandable that the above-mentioned processor can be a general-purpose processor, including a central processing unit (CPU), a network processor (NP), etc.; it can also be a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA) or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components.

[0093] It should also be noted that those skilled in the art can clearly understand that for the convenience and brevity of description, the specific working process of the system described above can refer to the corresponding process in the aforementioned method embodiment, and will not be repeated here. In the various embodiments provided in this application, the division of steps or modules in the system and method is only a logical function division. In actual implementation, there may be other division methods, for example, multiple modules or steps can be combined or integrated together, and a module or step can also be split.

[0094] The following example further illustrates the specific implementation of the blood-brain barrier water extraction rate imaging method based on arterial marking and speed selection shown in steps S1 to S2 of the present invention, and also demonstrates the technical effects that can be achieved.

[0095] Example:

[0096] The following describes a specific implementation of the blood-brain barrier water extraction rate imaging method based on arterial labeling and velocity selection, as shown in steps S1 and S2 above, along with examples to demonstrate its technical effects. This will facilitate a better understanding of the present invention for those skilled in the art. The specific implementations of steps S1 and S2 will not be detailed here. The following focuses on the specific parameter settings, some details of the method execution, and the resulting technical effects.

[0097] In the examples described below, all scans were performed using a Siemens Prisma 3.0T scanner. The WEFAST sequence was tested in eight young healthy volunteers (aged 24.88 ± 5.12 years, 4 females / 4 males). The specific scanning parameters (referred to as scanning parameter A for ease of description) were as follows: TR / TE = 9200 / 7.80 ms, FOV = 200 × 200 mm. 2 , the voxel size is 3.1×3.1mm 2 , the slice thickness is 10 mm, and the GRAPPA acceleration factor is 3. In the background suppression module, four non-selective inversion pulses are applied to suppress brain tissue signals and blood signals. The time between the four pulses and the EPI module is 2950 ms, 1180 ms, 420 ms, and 140 ms respectively. In the velocity selection module, the cutoff velocity (Vc) is set to 2 cm / s, and G RO The amplitude of the medium triangular gradient pulse was 20 mT / m and the duration was 0.75 ms. In the RF pulse train, the flip angle of each excitation pulse was 10°, and there were nine 10° excitation pulses in total, resulting in a 90° flip angle. Each 10° excitation pulse had an amplitude of 163.9 volts and a duration of 0.04 ms. A pair of 180° refocusing RF pulses was inserted between adjacent 10° excitation pulses, each with an amplitude of 196.997 volts and a duration of 1.2 ms. The velocity selection module finally applied a destruction gradient of 10.0 mT / m. The labeling duration for the entire WEFAST sequence was 4000 ms, and the post-labeling delay was 3000 ms.

[0098] Experiment 1: To test the accuracy and reliability of the WEFAST sequence and compare it with the existing WEPCAST ​​(water-extraction-with-phase-contrast-arterial-spin-tagging) sequence test results, the following scheme was used:

[0099] The test was repeated four times on eight volunteers, with each subject undergoing a full WEFAST and WEPCAST ​​scan. The subjects were first scanned twice in succession, then removed from the MRI machine, allowed to rest for one minute, and then scanned twice more in succession. Figure 8Figure A shows a representative control image, labeled image, and difference image obtained using WEPCAST ​​imaging for a representative participant, as well as a representative control image, labeled image, and difference image obtained using WEFAST imaging. To verify the accuracy of WEFAST measurements, we selected the water extraction rate and PS values ​​of the posterior superior sagittal sinus (SSS) corresponding to the WEPCAST ​​imaging layer for comparison and found that they showed a strong linear correlation with the water extraction rate values ​​(R = 0.59, P < 0.0001) and PS values ​​(R = 0.74, P < 0.0001) measured by WEPCAST ​​(e.g., Figure 8 B). Figure 8 C shows the Bland-Altman plots of E and PS obtained using the two methods. It can be seen that most points are distributed between the limits of agreement. The results of this experiment show that the WEFAST sequence shows high accuracy and reliability in measuring brain water extraction rate, and its results are highly consistent with the established WEPCAST ​​sequence.

[0100] Experiment 2: To test the repeatability of the WEFAST sequence, the following scheme was used:

[0101] We further analyzed the data from Experiment 1. Figure 9 Figure A shows the control image, labeled image, and difference image from two WEFAST scans of a representative participant. The coefficient of variation (CoV) was also calculated to assess the precision of the WEFAST measurements. Figure 9 As shown in Figure B, in WEFAST, the inter-time CoV of water extraction rate was 3.17±0.76%, the intra-time CoV was 3.11±0.67%, and the inter-time CoV of PS was 12.33±2.05%, and the intra-time CoV was 11.08±1.29%. In contrast, in WEPCAST, the inter-time CoV of water extraction rate was 3.08±0.73%, the intra-time CoV was 2.55±0.65%, and the inter-time CoV of PS was 12.07±2.19%, and the intra-time CoV was 9.06±1.56%. This indicates that WEFAST has high reproducibility and reliability for both large and small veins.

[0102] It should also be noted that those skilled in the art can clearly understand that for the convenience and brevity of description, the specific working process of the system described above can refer to the corresponding process in the aforementioned method embodiment, and will not be repeated here. In the various embodiments provided in this application, the division of steps or modules in the system and method is only a logical function division. In actual implementation, there may be other division methods, for example, multiple modules or steps can be combined or integrated together, and a module or step can also be split.

Claims

1. A blood-brain barrier water extraction rate imaging method based on arterial labeling and speed selection, characterized in that: The following steps are involved: S1: Applying an MRI sequence combining arterial spin labeling and velocity selection to the subject to be examined, alternating between labeling and control periods for signal acquisition; the MRI sequence employs pseudo-continuous arterial spin labeling (pCASL) technology to magnetize the carotid artery blood flow, and during a post-labeling delay period, a velocity selection module is introduced after the background suppression module to set the flowing blood spins within the target velocity range to a passband and the static tissue spins to a saturation band, thereby selectively extracting the arterial labeled blood signal in the vein and eliminating interference from brain tissue signals. Finally, the MRI signal is read out after the post-labeling delay period. S2: Calculate the magnetic resonance signal difference based on the collected magnetic resonance signals during the labeling period and the control period. Then, determine the water extraction fraction (E) of water molecules in arterial blood by brain tissue based on the magnetic resonance signal difference, and calculate the permeability-surface area product (PS).

2. The blood-brain barrier water extraction rate imaging method based on arterial labeling and speed selection according to claim 1, characterized in that: The speed selection module synchronously applies a speed selective saturation pulse sequence and a gradient pulse sequence based on Fourier transform; The velocity-selective saturation pulse sequence includes nine 10° excitation pulses and a pair of 180° refocusing radio frequency pulses is inserted between all two adjacent 10° excitation pulses. Both the 10° excitation pulse and the 180° refocusing radio frequency pulse are hard pulses, and all 16 180° refocusing radio frequency pulses adopt an MLEV-16 phase cycle scheme, with phases of 0°-0°-180°-180°-180°-0°-0°-180°-180°-0°-0°-180°-180°-0°. After the last 10° excitation pulse is applied, a destructive gradient for suppressing residual transverse magnetization is applied, and finally a recovery time is waited to restore all magnetization to the longitudinal direction. In the gradient pulse sequence, it is necessary to apply triangular gradient pulses with opposite polarities along a specified direction before and after each 180° refocusing radio frequency pulse.

3. The blood-brain barrier water extraction rate imaging method based on arterial labeling and speed selection according to claim 2, characterized in that: In the velocity selection module, the amplitude and duration of the triangular gradient pulse are pre-adjusted to adjust the cutoff velocity (Vc) of the velocity selection saturation band within the range of 2-30 cm / s. The cutoff velocity is used as the boundary to place the flowing blood spins with a velocity higher than the cutoff velocity in the pass-band, while the static tissue spins with a velocity lower than the cutoff velocity are placed in the saturation band, thereby preserving the flowing spin signal and suppressing the static background.

4. The blood-brain barrier water extraction rate imaging method based on arterial labeling and speed selection according to any one of claims 1 to 3, characterized in that: The magnetic resonance sequence includes a pre-saturation module, a labeling / control module, a post-labeling delay module, and a readout module; In the pre-saturation module, spatially selective saturation pulses are applied to reduce static tissue and unlabeled blood signals in the scanning area; In the labeling / control module, corresponding pulse trains and gradients are applied during the labeling and control periods, respectively, according to the pseudo-continuous arterial spin labeling (pCASL) technique, so that the magnetization of the arterial blood flowing into the brain is reversed during the labeling period to achieve the labeling effect, but the magnetization of the arterial blood flowing into the brain is not reversed during the control period; The post-labeling delay module includes a background suppression module and a speed selection module; the background suppression module is first executed to reduce the signal intensity of background tissue and unlabeled blood by applying non-selective inversion pulses that suppress brain tissue signals and blood signals; and the speed selection module is then executed to adjust the cutoff speed of the saturation band; In the readout module, single-shot echo planar imaging (EPI) is used to collect magnetic resonance signals of the target area in the brain; Preferably, the target area is the superior sagittal sinus (SSS) area. Preferably, in the magnetic resonance sequence, the labeling duration is set to 2000-4000 ms, and the post-labeling delay (PLD) is set to 1500 ms-5000 ms. Preferably, in the labeling / control module, during the labeling period, a pulse chain consisting of continuous short radio frequency pulses and gradient pulses are applied to reversely label the spins of water molecules in the arterial blood flowing through the labeling plane, wherein the duration of the short radio frequency pulses is 0.3 to 1 millisecond, the time interval between adjacent short radio frequency pulses is 0.5 to 1.5 milliseconds, and the amplitude of the gradient pulses is 5 to 20 mT / m; during the control period, no pulse chain is applied and only the same gradient pulses as those during the labeling period are applied.

5. The blood-brain barrier water extraction rate imaging method based on arterial labeling and speed selection according to claim 1, characterized in that: The water extraction fraction (E) of water molecules in arterial blood by brain tissue is determined based on the magnetic resonance signal difference and is calculated using the following model: Where: M0 is the equilibrium magnetization of blood, T 1,blood is the longitudinal relaxation time of blood, δ v is the arrival time of the spins to the target area, α is the labeling efficiency, c(t) is the arterial input function with time t as the independent variable, and satisfies when δ v <t<δ v c(t) = 1 when +τ, otherwise 0, where τ is the marking duration.

6. The blood-brain barrier water extraction rate imaging method based on arterial labeling and speed selection according to claim 1, characterized in that: The Renkin-Crone model was used to calculate the permeability-surface product (PS) based on the water extraction fraction (E). The calculation method is: PS=-f·ln(1-E) Where: f is the cerebral blood flow (CBF) of the subject to be tested.

7. A blood-brain barrier water extraction rate imaging system based on arterial labeling and speed selection, characterized in that: include: A data acquisition module is used to apply a magnetic resonance sequence to the object to be detected and alternately collect signals during the labeling period (Label) and the control period (Control); The magnetic resonance sequence uses pseudo-continuous arterial spin labeling (pCASL) technology to perform magnetization reversal on carotid arterial blood flow, and introduces a velocity selection module after the background suppression module during a post-labeling delay period to set the flowing blood spins within a target velocity range to a pass-band and the static tissue spins to a saturation-band, thereby selectively extracting the arterial labeled blood signal in the vein and eliminating interference from brain tissue signals. Finally, the magnetic resonance signal is read out after the post-labeling delay period expires. The calculation and processing module is used to calculate the magnetic resonance signal difference based on the collected labeling period magnetic resonance signals and the control period magnetic resonance signals, and then determine the water extraction fraction (E) of water molecules in arterial blood by brain tissue based on the magnetic resonance signal difference, and calculate the permeability-surface area product (PS).

8. A computer program product comprising a computer program / instructions, characterized in that When the computer program / instruction is executed by a processor, the blood-brain barrier water extraction rate imaging method based on arterial marking and speed selection as claimed in any one of claims 1 to 6 can be implemented.

9. A computer-readable storage medium, characterized in that The storage medium stores a computer program, and when the computer program is executed by a processor, the blood-brain barrier water extraction rate imaging method based on arterial marking and speed selection according to any one of claims 1 to 6 can be implemented.

10. A computer electronic device, characterized in that: including memory and processor; The memory is used to store computer programs; The processor is configured to implement the blood-brain barrier water extraction rate imaging method based on artery marking and speed selection as described in any one of claims 1 to 6 when executing the computer program.

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