Method, device, electronic device and medium for determining blood-brain barrier closing time

Abstract

The embodiment of the present invention discloses a method, device, electronic device and medium for determining the closing time of the blood-brain barrier, wherein the method comprises: in the process of opening the blood-brain barrier of the target brain area of ​​the target object by magnetic resonance-guided ultrasound, respectively obtaining the magnetic resonance longitudinal relaxation time spectrum corresponding to multiple contrast agent injection moments of the target brain area, determining the blood-brain barrier opening area of ​​the target brain area, the muscle tissue area corresponding to the blood-brain barrier opening area and the blood-brain barrier closing area; for each magnetic resonance longitudinal relaxation time spectrum, respectively determining the magnetic resonance longitudinal relaxation time of the blood-brain barrier opening area, the muscle tissue area and the blood-brain barrier closing area; determining the contrast agent concentration of each area based on the magnetic resonance longitudinal relaxation time of each area; determining the closing time of the blood-brain barrier opening area according to the contrast agent concentration of each area corresponding to multiple injection moments. The prediction of the blood-brain barrier opening recovery time is realized.

Description

Technical Field

[0001] The embodiments of the present invention relate to the field of biomedical technology, and in particular to a method, device, electronic device and medium for determining the closing time of a blood-brain barrier. Background Art

[0002] The blood-brain barrier is a physiological barrier between brain tissue and the peripheral circulatory system. This structure can prevent harmful substances in the circulatory system from entering the brain tissue, and has important biological significance for maintaining the stability of the brain environment and the normal physiological state of the central nervous system. At the same time, for the treatment of brain diseases, the blood-brain barrier also restricts large molecule therapeutic drugs from entering the central nervous system to take effect, and is a major obstacle to drug administration to the central nervous system. At present, under the guidance of magnetic resonance imaging, ultrasound combined with microbubbles can temporarily and non-invasively open the blood-brain barrier at a fixed point, allowing drugs to enter the brain area and improve the efficiency of drug action.

[0003] Although the feasibility and effectiveness of MRI-guided ultrasound-assisted blood-brain barrier opening technology have been verified in various animal models and even in human patients, the clinical transformation of this technology still faces safety challenges. One of the important reasons is that it has not been effectively determined how long it will take for the blood-brain barrier to recover after opening, and the closing time of the blood-brain barrier is a safety issue of great concern in clinical practice. Summary of the invention

[0004] The embodiments of the present invention provide a method, device, electronic device and medium for determining the closing time of the blood-brain barrier, so as to predict the closing time of the blood-brain barrier.

[0005] In a first aspect, an embodiment of the present invention provides a method for determining blood-brain barrier closing time, the method comprising:

[0006] In the process of opening the blood-brain barrier of the target brain region of the target object by magnetic resonance-guided ultrasound, respectively obtaining magnetic resonance longitudinal relaxation time maps of the target brain region corresponding to multiple contrast agent injection moments, wherein the magnetic resonance longitudinal relaxation time map corresponding to each of the contrast agent injection moments includes a magnetic resonance longitudinal relaxation time map at a moment before the contrast agent is injected and a magnetic resonance longitudinal relaxation time map at a moment after the contrast agent is injected;

[0007] Determining a blood-brain barrier open area of ​​the target brain region, a muscle tissue area corresponding to the blood-brain barrier open area, and a blood-brain barrier closed area corresponding to the blood-brain barrier open area;

[0008] For each magnetic resonance longitudinal relaxation time spectrum, respectively determining a first magnetic resonance longitudinal relaxation time of the open region of the blood-brain barrier, a second magnetic resonance longitudinal relaxation time of the muscle tissue region, and a third magnetic resonance longitudinal relaxation time of the closed region of the blood-brain barrier;

[0009] Determine the contrast agent concentration of the open area of ​​the blood-brain barrier based on the first magnetic resonance longitudinal relaxation time, determine the muscle contrast agent concentration of the muscle tissue area based on the second magnetic resonance longitudinal relaxation time, and determine the closed contrast agent concentration of the blood-brain barrier closed area based on the third magnetic resonance longitudinal relaxation time;

[0010] The closing time of the open area of ​​the blood-brain barrier is determined according to the open area contrast agent concentration, the muscle contrast agent concentration and the closed contrast agent concentration corresponding to multiple contrast agent injection moments.

[0011] In a second aspect, an embodiment of the present invention further provides a device for determining blood-brain barrier closing time, the device comprising:

[0012] A magnetic resonance spectrum acquisition module is used to respectively acquire magnetic resonance longitudinal relaxation time spectra corresponding to multiple contrast agent injection moments of the target brain region in the process of opening the blood-brain barrier of the target brain region of the target object by magnetic resonance-guided ultrasound, wherein the magnetic resonance longitudinal relaxation time spectrum corresponding to each of the contrast agent injection moments includes a magnetic resonance longitudinal relaxation time spectrum at a moment before the contrast agent is injected and a magnetic resonance longitudinal relaxation time spectrum at a moment after the contrast agent is injected;

[0013] A region determination module, used to determine the blood-brain barrier open region of the target brain region, the muscle tissue region corresponding to the blood-brain barrier open region, and the blood-brain barrier closed region corresponding to the blood-brain barrier open region;

[0014] A magnetic resonance longitudinal relaxation time determination module, for determining, for each magnetic resonance longitudinal relaxation time spectrum, a first magnetic resonance longitudinal relaxation time of the open region of the blood-brain barrier, a second magnetic resonance longitudinal relaxation time of the muscle tissue region, and a third magnetic resonance longitudinal relaxation time of the closed region of the blood-brain barrier;

[0015] a contrast agent concentration determination module, configured to determine an open area contrast agent concentration of the open area of ​​the blood-brain barrier based on the first magnetic resonance longitudinal relaxation time, determine a muscle contrast agent concentration of the muscle tissue area based on the second magnetic resonance longitudinal relaxation time, and determine a closed contrast agent concentration of the closed area of ​​the blood-brain barrier based on the third magnetic resonance longitudinal relaxation time;

[0016] The blood-brain barrier closing time determination module is used to determine the closing time of the open area of ​​the blood-brain barrier according to the open area contrast agent concentration, the muscle contrast agent concentration and the closed contrast agent concentration corresponding to multiple contrast agent injection moments.

[0017] In a third aspect, an embodiment of the present invention further provides an electronic device, the electronic device comprising:

[0018] one or more processors;

[0019] a storage device for storing one or more programs,

[0020] When the one or more programs are executed by the one or more processors, the one or more processors implement the method for determining the blood-brain barrier closing time provided by any embodiment of the present invention.

[0021] In a fourth aspect, an embodiment of the present invention further provides a computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements the method for determining the blood-brain barrier closing time provided by any embodiment of the present invention.

[0022] The technical solution of the embodiment of the present invention is to obtain magnetic resonance longitudinal relaxation time maps of the target brain area corresponding to multiple contrast agent injection moments in the process of opening the blood-brain barrier of the target brain area of ​​the target object through magnetic resonance-guided ultrasound, and to obtain the magnetic resonance longitudinal relaxation time map at each moment to obtain the data of the target brain area at each moment, and then determine the blood-brain barrier opening area of ​​the target brain area, the muscle tissue area corresponding to the blood-brain barrier opening area, and the blood-brain barrier closed area corresponding to the blood-brain barrier opening area. Taking into account the diffusion effect of the contrast agent in the blood vessels, the muscle tissue area and the blood-brain barrier closed area corresponding to the blood-brain barrier opening area can be determined, laying a foundation for accurately predicting the recovery time of the blood-brain barrier opening area. For each magnetic resonance longitudinal relaxation time spectrum, the first magnetic resonance longitudinal relaxation time of the open area of ​​the blood-brain barrier, the second magnetic resonance longitudinal relaxation time of the muscle tissue area and the third magnetic resonance longitudinal relaxation time of the closed area of ​​the blood-brain barrier are determined respectively, and then the open area contrast agent concentration of the open area of ​​the blood-brain barrier is determined based on the first magnetic resonance longitudinal relaxation time, the muscle contrast agent concentration of the muscle tissue area is determined based on the second magnetic resonance longitudinal relaxation time, and the closed contrast agent concentration of the closed area of ​​the blood-brain barrier is determined based on the third magnetic resonance longitudinal relaxation time. Based on the contrast agent concentrations of the three areas, finally, the closing time of the open area of ​​the blood-brain barrier is determined according to the open area contrast agent concentrations, muscle contrast agent concentrations and closed contrast agent concentrations corresponding to multiple contrast agent injection moments. The above technical solution calculates the contrast agent concentrations of the open area of ​​the blood-brain barrier, the muscle tissue area and the closed area of ​​the blood-brain barrier at each contrast agent moment through the magnetic resonance longitudinal relaxation time spectrum at each contrast agent moment, and then determines the closing time of the open area of ​​the blood-brain barrier, which solves the problem in the prior art that the recovery time of the blood-brain barrier after opening cannot be predicted, and achieves the effect of accurately predicting the closing time of the blood-brain barrier. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the technical solutions of the exemplary embodiments of the present invention, the following briefly introduces the drawings required to describe the embodiments. Obviously, the drawings introduced are only drawings of a part of the embodiments to be described in the present invention, rather than all the drawings. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0024] Figure 1 A schematic flow chart of a method for determining blood-brain barrier closing time provided in Embodiment 1 of the present invention;

[0025] Figure 2 This is a flow chart of a method for determining blood-brain barrier closing time provided in Embodiment 2 of the present invention;

[0026] Figure 3 This is a schematic diagram of obtaining a magnetic resonance longitudinal relaxation time spectrum in a method for determining blood-brain barrier closing time provided in Example 2 of the present invention;

[0027] Figure 4 is a flow chart of an optional embodiment of a method for determining blood-brain barrier closing time provided in Embodiment 2 of the present invention;

[0028] Figure 5 This is a schematic diagram of the structure of a device for determining blood-brain barrier closing time provided in Embodiment 3 of the present invention;

[0029] Figure 6 This is a schematic diagram of the structure of an electronic device provided in Embodiment 4 of the present invention. DETAILED DESCRIPTION

[0030] The present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments. It is to be understood that the specific embodiments described herein are only used to explain the present invention, rather than to limit the present invention. It should also be noted that, for ease of description, only parts related to the present invention, rather than all structures, are shown in the accompanying drawings.

[0031] It should also be noted that, for ease of description, only the part relevant to the present invention but not all content is shown in the accompanying drawings. It should be mentioned before discussing exemplary embodiments in more detail that some exemplary embodiments are described as processing or methods depicted as flow charts. Although the flow chart describes each operation (or step) as sequential processing, many operations therein can be implemented in parallel, concurrently or simultaneously. In addition, the order of each operation can be rearranged. When its operation is completed, the processing can be terminated, but it can also have additional steps not included in the accompanying drawings. The processing can correspond to methods, functions, procedures, subroutines, subprograms, etc.

[0032] Embodiment 1

[0033] Figure 1 This is a flow chart of a method for determining the closing time of the blood-brain barrier provided in the first embodiment of the present invention. This embodiment can be applied to predicting how long it takes for the blood-brain barrier to recover after opening. The method can be executed by a device for determining the closing time of the blood-brain barrier. The device can be implemented by software and / or hardware and can be configured in a terminal and / or server to implement the method for determining the closing time of the blood-brain barrier in the embodiment of the present invention.

[0034] like Figure 1 As shown, the method of this embodiment may specifically include:

[0035] S110. In the process of opening the blood-brain barrier of the target brain area of ​​the target object through magnetic resonance-guided ultrasound, magnetic resonance longitudinal relaxation time maps of the target brain area corresponding to multiple contrast agent injection moments are respectively obtained, wherein the magnetic resonance longitudinal relaxation time map corresponding to each of the contrast agent injection moments includes the magnetic resonance longitudinal relaxation time map at a moment before the contrast agent is injected and the magnetic resonance longitudinal relaxation time map at a moment after the contrast agent is injected.

[0036] Among them, the target object can be understood as the object whose blood-brain barrier is to be opened by magnetic resonance-guided ultrasound. The target brain area can be understood as the brain area for which the magnetic resonance longitudinal relaxation time map is to be obtained. The target brain area includes but is not limited to the blood-brain barrier open area, the muscle tissue area corresponding to the blood-brain barrier open area, and the blood-brain barrier closed area corresponding to the blood-brain barrier open area. The contrast agent can be understood as a paramagnetic agent used to enhance the image contrast effect during magnetic resonance imaging. After the contrast agent is injected, the intensity of the tissue signal can be indirectly changed by the relaxation speed of the tissue around the image, thereby increasing the contrast of the tissue or organ.

[0037] After opening the blood-brain barrier of the target brain region of the target subject by magnetic resonance-guided ultrasound, an equal amount of the same contrast agent can be injected into the target brain region at multiple contrast agent injection times. The time intervals between the contrast agent injection times corresponding to two adjacent contrast agent injections can be the same or different, and the specific injection times and specific values ​​of the time intervals of the multiple contrast agent injection times are not specifically limited here.

[0038] Exemplarily, the contrast agent may be injected intravenously, for example, intravenously into a limb of the target subject.

[0039] There are many ways to open the blood-brain barrier. For example, under the guidance of magnetic resonance imaging, ultrasound combined with microbubbles can temporarily and non-invasively open the blood-brain barrier at a fixed point. This method can control the opening range of the blood-brain barrier, reduce damage to brain tissue, and easily obtain the location of the open area of ​​the blood-brain barrier.

[0040] In the magnetic resonance phenomenon, atomic nuclei resonate and are in a high-energy state. When the radio frequency pulse stops, they quickly return to a low-energy state. The recovery process is called the relaxation process. The longitudinal relaxation time is usually the time required for the longitudinal magnetization intensity component to return to the equilibrium state, which can also be represented by T1. Among them, the size of T1 depends on the external magnetic field and the interaction between the proton and the surrounding environment (that is, the nature of the tissue). It is an inherent characteristic of the tissue. After the external magnetic field is given, the T1 values ​​of different tissues have corresponding fixed values, and there are large differences.

[0041] Specifically, in the process of opening the blood-brain barrier of the target brain area of ​​the target object through magnetic resonance-guided ultrasound, it is necessary to inject contrast agent into the target brain area multiple times, and measure the longitudinal relaxation time spectrum T1 of the target brain area before and after the injection of the contrast agent, respectively. The measurement method can be, for example, inversion recovery technology, saturation recovery method and variable flip angle magnetic resonance imaging technology.

[0042] In clinical applications, magnetic resonance T1 quantitative methods can use perfusion and permeability measurements, mainly using T1-weighted dynamic contrast-enhanced imaging (DCE-MRI) sequences to detect and characterize lesions and tumors, monitor treatment, evaluate organ function, etc. Through these techniques, it is possible to detect signal intensity differences caused by changes in contrast agent concentration and evaluate parameters of interest in a semi-quantitative manner.

[0043] Considering that the MRI signal intensity not only reflects the contrast agent concentration, but also depends on the intrinsic tissue properties (T1, T2, and spin density), imaging parameters (such as flip angle (F A ), repetition time (T R ), echo time (T E )) and hardware of MRI scanners (e.g., receiver gain), making it difficult to standardize DCE-MRI technology. Therefore, a fast and accurate T1 spectrum test technology can be used to quantitatively describe the distribution and dynamic process of paramagnetic contrast agents. By dynamically measuring T1, the changes in contrast agent concentration can be directly quantitatively described.

[0044] Optionally, respectively acquiring magnetic resonance longitudinal relaxation time maps of the target brain region corresponding to multiple contrast agent injection moments includes: acquiring magnetic resonance longitudinal relaxation time maps of the target brain region corresponding to multiple contrast agent injection moments based on variable flip angle magnetic resonance imaging technology.

[0045] Specifically, in clinical MRI applications, contrast agents can be injected into the target brain area using perfusion and permeability measurements. Due to the inherent characteristics of different tissues, the longitudinal relaxation times of different tissues have corresponding fixed values ​​after the external magnetic field is given, and there are large differences. Therefore, the distribution and dynamic process of contrast agents in different tissues can be quantitatively described based on the magnetic resonance longitudinal relaxation time spectrum testing technology. For example, variable flip angle magnetic resonance imaging technology can be used to achieve fast-read longitudinal relaxation time quantification, combined with radio frequency B1 field spectrum technology to compensate for the spatial variation of the emission angle, and a high-precision longitudinal relaxation time spectrum can be obtained within the effective acquisition time.

[0046] S120, determining the blood-brain barrier open area of ​​the target brain area, the muscle tissue area corresponding to the blood-brain barrier open area, and the blood-brain barrier closed area corresponding to the blood-brain barrier open area.

[0047] Among them, the blood-brain barrier open area can be understood as the brain area where the blood-brain barrier is opened by magnetic resonance guided ultrasound. The muscle tissue area corresponding to the blood-brain barrier open area can be understood as the muscle tissue area adjacent to the blood-brain barrier open area. The blood-brain barrier closed area can be understood as the brain area where the blood-brain barrier is not opened. In an embodiment of the present invention, optionally, the blood-brain barrier closed area corresponding to the blood-brain barrier open area can be understood as the brain area where the blood-brain barrier is not opened, which is located in the contralateral hemisphere of the brain and is structurally symmetrical with the blood-brain barrier open area. Among them, the contralateral hemisphere of the brain can be understood as the brain hemisphere on the different side of the blood-brain barrier open area.

[0048] Optionally, a marking operation input by a user is received to mark and determine the open area of ​​the blood-brain barrier of the target brain region, the muscle tissue area corresponding to the open area of ​​the blood-brain barrier, and the closed area of ​​the blood-brain barrier corresponding to the open area of ​​the blood-brain barrier, and the open area of ​​the blood-brain barrier, the muscle tissue area, and the closed area of ​​the blood-brain barrier of the target brain region are determined based on the marking operation.

[0049] At the same time, considering that ultrasound will inevitably affect the tissues near the open area of ​​the blood-brain barrier, the muscle tissue area corresponding to the open area of ​​the blood-brain barrier can also be determined.

[0050] S130. For each magnetic resonance longitudinal relaxation time spectrum, respectively determine a first magnetic resonance longitudinal relaxation time of the open region of the blood-brain barrier, a second magnetic resonance longitudinal relaxation time of the muscle tissue region, and a third magnetic resonance longitudinal relaxation time of the closed region of the blood-brain barrier.

[0051] It is understandable that the concentration of contrast agent in the blood vessel is proportional to the blood vessel signal intensity. The greater the amount of contrast agent injected, the higher the contrast agent concentration in the blood vessel and the stronger the blood vessel signal intensity. When the contrast agent concentration is high, the magnetic resonance signal is prone to saturation. In the embodiment of the present invention, the contrast agent concentration is calculated by the magnetic resonance T1 spectrum, which can effectively avoid the saturation of the magnetic resonance signal.

[0052] Among them, the magnetic resonance system has a variety of scanning sequences for T1 atlas scanning. Optionally, through the traditional gold standard method, a series of different inversion time T1 scans are performed one by one, wherein the signal intensity of each different T1 presents an exponential distribution, and then, mathematical fitting is performed based on the magnetic resonance signal intensity formula to calculate the T1 value of each voxel. Among them, the magnetic resonance signal intensity formula is as follows:

[0053] S(t)=A·abs(1-2·exp(-t / T1)+exp(-T R / T1))+C

[0054] Where S(t) represents the magnetic resonance signal intensity measured by flipping at time t using the flip recovery magnetic resonance imaging sequence; A is the magnetic resonance magnetization vector signal intensity at the initial moment of the saturation state under normal circumstances; abs represents the absolute value operation; exp is the exponential operation symbol expression; T1 represents the longitudinal magnetic resonance time; T R represents the repetition time of the magnetic resonance scanning sequence; C represents the background noise average signal collected by the magnetic resonance coil.

[0055] Variable flip angle (VFA) MRI technology can achieve fast reading of T1 quantification. Combined with radiofrequency B1 field mapping technology to compensate for the spatial variation of the emission angle, high-precision T1 maps can be obtained within the effective acquisition time. VFA technology is a continuous T1-weighted damaged gradient echo sequence under different flip angles. Its MRI signal intensity formula is composed of the initial MRI intensity M0, tissue relaxation parameters T1 and T2, and echo time T E , repetition time T R and the flip angle α.

[0056]

[0057] Wherein, S(α) may represent the acquired magnetic resonance signal intensity, α may represent the magnetic resonance radio frequency flip angle, and M0 may represent the initial magnetic resonance signal intensity after the saturation state.

[0058] The above formula can be further expanded into a linear equation as follows:

[0059]

[0060] Among them, E1 in the above formula = exp(-T R / T1),E2=exp(-T E / T2), T1 represents the longitudinal magnetic relaxation time of magnetic resonance, and T2 represents the transverse relaxation time of magnetic resonance; T R represents the repetition time of the MRI scanning sequence, T E Represents the echo time of the magnetic resonance scanning sequence, T R and T E is a fixed scanning parameter of magnetic resonance; S(α) can represent the acquired magnetic resonance signal intensity, α can represent the magnetic resonance radio frequency flip angle, and M0 can represent the initial magnetic resonance signal intensity after the saturation state.

[0061] The magnetic resonance signal intensity obtained by testing at different inversion angles can be understood as a linear equation with E1 as the slope and M0(1-E1)*E2 as the intercept.

[0062] When the longitudinal magnetization reaches a steady state in each scan, the transverse magnetization is completely destroyed and B1 is uniform, the quantitative value of T1 can be obtained.

[0063] Specifically, the T1 value of the magnetic resonance T1 spectrum can be calculated by the following formula:

[0064]

[0065] Optionally, the longitudinal relaxation is brought to a saturated state by continuous excitation in front of the collector, and then excitation and collection are performed; the transverse relaxation residue is eliminated by radio frequency destruction or gradient destruction, and the spatial uniformity of the inversion angle is compensated by B1 mapping technology.

[0066] Taking into account the incompleteness of the new blood vessels, the contrast agent injected into the blood vessels of the open area of ​​the blood-brain barrier may diffuse into the surrounding muscle tissue, resulting in a shortened longitudinal relaxation time of the muscle tissue around the open area of ​​the blood-brain barrier. According to the inherent characteristics of different tissues, the open area, muscle tissue area and closed area of ​​the blood-brain barrier in the target brain area can be measured separately to obtain the corresponding magnetic resonance longitudinal relaxation times of the three areas.

[0067] S140. Determine the contrast agent concentration in the open area of ​​the blood-brain barrier based on the first magnetic resonance longitudinal relaxation time, determine the muscle contrast agent concentration in the muscle tissue area based on the second magnetic resonance longitudinal relaxation time, and determine the closed contrast agent concentration in the closed area of ​​the blood-brain barrier based on the third magnetic resonance longitudinal relaxation time.

[0068] Generally, since contrast agents cannot pass through the blood-brain barrier to reach tissue areas when the blood-brain barrier is intact, the open area of ​​the blood-brain barrier in the target brain area can be determined based on the change in contrast agent concentration over time in the open area of ​​the blood-brain barrier, combined with the change in contrast agent concentration over time in the muscle tissue area corresponding to the open area of ​​the blood-brain barrier and the closed area of ​​the blood-brain barrier.

[0069] Specifically, magnetic resonance technology can be used to detect the difference in tissue signal intensity caused by contrast agent concentration. According to the intensity of the tissue signal, dynamic measurement of the longitudinal relaxation time can directly and quantitatively describe the change in contrast agent concentration, thereby determining the contrast agent concentration corresponding to the first magnetic resonance longitudinal relaxation time, the second magnetic resonance longitudinal relaxation time, and the third magnetic resonance longitudinal relaxation time.

[0070] Optionally, the contrast agent concentration of a certain voxel or a certain region at a certain time after the contrast agent is injected is determined based on the relaxation rate of the contrast agent, the first magnetic resonance longitudinal relaxation time of the region when the contrast agent is not injected, and the first magnetic resonance longitudinal relaxation time of the region at this time. Specifically, it can be determined based on the following formula:

[0071] C(t)=1 / R1·(1 / T1(t)-1 / T 10 )

[0072] Where C(t) represents the open area contrast agent concentration of the target area at time t, R1 represents the relaxation rate of the contrast agent, and T 10 represents the first magnetic resonance longitudinal relaxation time of the target region when no contrast agent is injected, and T1(t) represents the first magnetic resonance longitudinal relaxation time of the target region at time t.

[0073] Before ultrasound opening of the blood-brain barrier and injection of contrast agent, an MRI scan test can be performed on the target brain area to obtain a set of MRI quantitative parameter baselines. Based on the MRI quantitative parameter baselines, the first MRI longitudinal relaxation time of the blood-brain barrier open area, muscle tissue area and blood-brain barrier closed area when no contrast agent is injected can be determined respectively.

[0074] Exemplarily, determining the open area contrast agent concentration of the open area of ​​the blood-brain barrier based on the first magnetic resonance longitudinal relaxation time includes: determining the open area contrast agent concentration of the open area of ​​the blood-brain barrier based on the following formula and the first magnetic resonance longitudinal relaxation time:

[0075] C f (t) = 1 / R1·(1 / T 1f (t)-1 / T 10f )

[0076] Among them, C f (t) represents the contrast agent concentration in the open area of ​​the blood-brain barrier at time t, R1 represents the relaxation rate of the contrast agent, T 10f represents the first MRI longitudinal relaxation time of the open area of ​​the blood-brain barrier when no contrast agent is injected, T 1f (t) represents the first magnetic resonance longitudinal relaxation time of the open area of ​​the blood-brain barrier at time t.

[0077] Similarly, the muscle contrast agent concentration of the muscle tissue region may be determined based on the following formula and the second magnetic resonance longitudinal relaxation time:

[0078] C m (t) = 1 / R1·(1 / T 1m (t)-1 / T 10m )

[0079] Among them, C m (t) represents the open area contrast agent concentration of the muscle tissue area at time t, R1 represents the relaxation rate of the contrast agent, T 10m represents the first magnetic resonance longitudinal relaxation time of the muscle tissue region without contrast agent injection, T 1m(t) represents the first magnetic resonance longitudinal relaxation time of the muscle tissue region at time t.

[0080] Similarly, the contrast agent concentration in the blood-brain barrier closed area may be determined based on the following formula and the third magnetic resonance longitudinal relaxation time:

[0081] C c (t) = 1 / R1·(1 / T 1c (t)-1 / T 10c )

[0082] Among them, C c (t) represents the contrast agent concentration in the open area of ​​the closed area of ​​the blood-brain barrier at time t, R1 represents the relaxation rate of the contrast agent, T 10c represents the first magnetic resonance longitudinal relaxation time of the blood-brain barrier closed region when no contrast agent is injected, T 1c (t) represents the first magnetic resonance longitudinal relaxation time of the blood-brain barrier closed region at time t.

[0083] S150, determining the closing time of the open area of ​​the blood-brain barrier according to the open area contrast agent concentration, the muscle contrast agent concentration, and the closed contrast agent concentration corresponding to multiple contrast agent injection moments.

[0084] Taking into account the differences in the changes in the concentration of contrast agents in different areas at different times, as well as the diffusion effect of contrast agents in blood vessels, the contrast agent concentration in the open area of ​​the blood-brain barrier can be related to the vascular contrast agent concentration corresponding to the open area of ​​the blood-brain barrier. Among them, for the convenience of calculation, the vascular contrast agent concentration can be determined by the muscle contrast agent concentration in the adjacent muscle tissue area. Therefore, in an embodiment of the present invention, the influence of the vascular contrast agent concentration on the contrast agent concentration in the open area can be considered when determining the contrast agent concentration in the open area. Considering that after the contrast agent is injected into the brain area, even if the blood-brain barrier is not opened, there is a certain degree of metabolism and attenuation, and its concentration will also change. Therefore, the closed contrast agent concentration in the closed area of ​​the blood-brain barrier can be used as a reference standard for whether the open area of ​​the blood-brain barrier has been restored.

[0085] Specifically, the contrast agent concentration in the open area, muscle tissue area and closed area of ​​the blood-brain barrier at multiple contrast agent injection times can be used to determine the jump amplitude of the contrast agent concentration in the area before and after the contrast agent injection at each contrast agent injection time, as well as the attenuation coefficient of the contrast agent concentration between different contrast agent injection times. Furthermore, the blood-brain barrier closing time is predicted based on the jump amplitude and attenuation coefficient of the contrast agent concentration corresponding to the open area, muscle tissue area and closed area of ​​the blood-brain barrier.

[0086] The above technical solution calculates the contrast agent concentrations of the open area of ​​the blood-brain barrier, the muscle tissue area and the closed area of ​​the blood-brain barrier at each contrast agent moment through the magnetic resonance longitudinal relaxation time spectrum at each contrast agent moment, and then determines the closing time of the open area of ​​the blood-brain barrier, which solves the problem in the prior art that the recovery time of the blood-brain barrier after opening cannot be predicted, and achieves the effect of accurately predicting the closing time of the blood-brain barrier.

[0087] Embodiment 2

[0088] Figure 2 Flow chart of the method for determining the blood-brain barrier closing time provided in the second embodiment of the present invention; Figure 2 As shown, this embodiment is based on any optional technical solution in the embodiments of the present invention, and optionally, the closing time of the open area of ​​the blood-brain barrier is determined according to the open area contrast agent concentration, the muscle contrast agent concentration and the closed contrast agent concentration, including: fitting and solving a pre-constructed muscle contrast agent concentration attenuation model according to the muscle contrast agent concentrations corresponding to multiple contrast agent injection moments, to obtain the attenuation time coefficient of the muscle contrast agent concentration and the muscle jump amplitude of the muscle contrast agent concentration at each contrast agent injection moment; fitting and solving a pre-constructed open area recovery model according to the open area contrast agent concentrations, the attenuation time coefficient, and the muscle jump amplitude corresponding to multiple contrast agent injection moments, to obtain the recovery time coefficient of the open area of ​​the blood-brain barrier and the open jump amplitude of the open area contrast agent concentration at each contrast agent injection moment; determining the closing time of the open area of ​​the blood-brain barrier based on the closed contrast agent concentration, the open jump amplitude and the recovery time coefficient.

[0089] like Figure 2 As shown, the method of this embodiment may specifically include:

[0090] S210. In the process of opening the blood-brain barrier of the target brain area of ​​the target object through magnetic resonance-guided ultrasound, magnetic resonance longitudinal relaxation time maps of the target brain area corresponding to multiple contrast agent injection moments are respectively obtained, wherein the magnetic resonance longitudinal relaxation time map corresponding to each of the contrast agent injection moments includes the magnetic resonance longitudinal relaxation time map at a moment before the contrast agent is injected and the magnetic resonance longitudinal relaxation time map at a moment after the contrast agent is injected.

[0091] S220, determining the blood-brain barrier open area of ​​the target brain region, the muscle tissue area corresponding to the blood-brain barrier open area, and the blood-brain barrier closed area corresponding to the blood-brain barrier open area of ​​the target open area.

[0092] S230, for each magnetic resonance longitudinal relaxation time spectrum, respectively determine a first magnetic resonance longitudinal relaxation time of the open area of ​​the blood-brain barrier, a second magnetic resonance longitudinal relaxation time of the muscle tissue area, and a third magnetic resonance longitudinal relaxation time of the closed area of ​​the blood-brain barrier.

[0093] S240. Determine the contrast agent concentration in the open area of ​​the blood-brain barrier based on the first magnetic resonance longitudinal relaxation time, determine the muscle contrast agent concentration in the muscle tissue area based on the second magnetic resonance longitudinal relaxation time, and determine the closed contrast agent concentration in the closed area of ​​the blood-brain barrier based on the third magnetic resonance longitudinal relaxation time.

[0094] S250. Fit and solve a pre-constructed muscle contrast agent concentration attenuation model according to the muscle contrast agent concentrations corresponding to multiple contrast agent injection moments to obtain the attenuation time coefficient of the muscle contrast agent concentration and the muscle jump amplitude of the muscle contrast agent concentration at each contrast agent injection moment.

[0095] Optionally, the muscle contrast agent concentration attenuation model is:

[0096] C m (t) = Bp·e -μt *u(t)

[0097] Among them, C m (t) represents the muscle contrast agent concentration in the muscle tissue area at time t, Bp represents the muscle jump amplitude of the muscle contrast agent concentration at each contrast agent injection moment, · represents multiplication operation, μ represents the attenuation time coefficient of the muscle contrast agent concentration, * represents convolution operation, and u(t) represents the unit input function.

[0098] It should be noted that the value of u(t) can be 0 or 1. In the embodiment of the present invention, when the contrast agent is injected, or at the moment of contrast agent injection, the value of u(t) is 1, otherwise, the value of u(t) is 0.

[0099] S260. Fit and solve the pre-constructed open area recovery model according to the open area contrast agent concentration, the attenuation time coefficient, and the muscle jump amplitude corresponding to multiple contrast agent injection moments, to obtain the recovery time coefficient of the open area of ​​the blood-brain barrier and the open jump amplitude of the contrast agent concentration in the open area at each contrast agent injection moment.

[0100] Generally, the blood-brain barrier reaches its maximum opening degree after the end of the ultrasound effect, and then gradually recovers. In the embodiment of the present invention, it can be assumed that the blood-brain barrier opening degree is an exponential decay process. Further, the attenuation coefficient can be solved by experimental data fitting and multiple angiography measurements.

[0101] Specifically, the change in the contrast agent concentration in the open area of ​​the blood-brain barrier first undergoes a gathering process, which then weakens after reaching a peak value. Each time the contrast agent is injected, the contrast agent concentration in the open area of ​​the blood-brain barrier has an impulse response, and this impulse response is related to the single increase in the injection contrast agent concentration and the current recovery state of the blood-brain barrier, as well as the difference between the current intravascular contrast agent concentration and the contrast concentration in the open area.

[0102] Wherein, the open area recovery model is constructed based on the muscle contrast agent concentration attenuation model.

[0103] Optionally, the open area recovery model is:

[0104]

[0105] Among them, C f (t) represents the contrast agent concentration in the open area of ​​the blood-brain barrier at time t, Ap represents the muscle jump amplitude of the contrast agent concentration in the open area at each contrast agent injection time, · represents multiplication operation, λ represents the recovery time coefficient of the open area of ​​the blood-brain barrier, * represents convolution operation, u(t) represents the unit input function, b is a constant, bC m (t) represents the vascular contrast agent concentration.

[0106] Specifically, according to the open area contrast agent concentration C corresponding to multiple contrast agent injection moments f (t), the attenuation time coefficient μ, and the muscle jump amplitude Bp are fitted and solved to obtain the recovery time coefficient λ of the open area of ​​the blood-brain barrier and the open jump amplitude Ap of the contrast agent concentration in the open area at each contrast agent injection moment.

[0107] S270, determining the closing time of the open area of ​​the blood-brain barrier based on the closing contrast agent concentration, the opening jump amplitude and the recovery time coefficient.

[0108] The closed contrast agent concentration is determined based on the closed contrast agent concentration attenuation model. Similarly, the closed contrast agent concentration attenuation model can also be constructed based on an exponential decay function.

[0109] Optionally, the closed contrast agent concentration attenuation model is:

[0110] C c (t) = Cp·e -υt *u(t)

[0111] Among them, C c(t) represents the muscle contrast agent concentration of the muscle tissue area at time t, Cp represents the muscle jump amplitude of the muscle contrast agent concentration at each contrast agent injection moment, · represents multiplication operation, υ represents the decay time coefficient of the muscle contrast agent concentration, * represents convolution operation, and u(t) represents the unit input function.

[0112] Optionally, the closing time of the open area of ​​the blood-brain barrier can be determined according to the closing contrast agent concentration, the opening jump amplitude and the recovery time coefficient.

[0113] Specifically, the closing time of the open area of ​​the blood-brain barrier is determined based on the following formula and the concentration of the closed contrast agent, the open jump amplitude and the recovery time coefficient:

[0114]

[0115] Among them, T c represents the closing time of the open area of ​​the blood-brain barrier, C c (t) is the closed contrast agent concentration of the blood-brain barrier closed area at time t, Indicates that the blood-brain barrier closed area at t = T c The closed contrast agent concentration at the moment, Ap represents the muscle jump amplitude of the contrast agent concentration in the open area at each contrast agent injection moment, · represents multiplication operation, and λ represents the recovery time coefficient of the open area of ​​the blood-brain barrier.

[0116] Figure 3 This is a schematic diagram of obtaining a magnetic resonance longitudinal relaxation time spectrum in a method for determining blood-brain barrier closing time provided in Example 2 of the present invention. Figure 4 This is a flow chart of an optional embodiment of a method for determining blood-brain barrier closing time provided in the second embodiment.

[0117] For example, Figure 3 and Figure 4 As shown, before opening the blood-brain barrier with MRI-guided ultrasound, a set of MRI quantitative parameter baselines (i.e., QMRI baseline) are tested, and then the blood-brain barrier (BBB) ​​of the target subject is opened with ultrasound combined with microbubbles (i.e., US+MB), and contrast agents (i.e., Figure 3 After the first opening of the blood-brain barrier, the first quantitative magnetic resonance measurement is performed. mRepresents the time of contrast agent injection. Specifically, at time t1=0, the first contrast agent injection is performed, and magnetic resonance T1 dynamic tests QMRI base1 and QMRI measure1 are performed before and after time t1=0, respectively, to obtain the T1 magnetic resonance longitudinal relaxation time T1 of the open area, muscle tissue area and closed area of ​​the blood-brain barrier corresponding to time t1. At time t2, the same amount of the same contrast agent as that at time t1 is injected, and then, the second magnetic resonance T1 dynamic test QMRI base2 and QMRI measure2 are performed to obtain the T1 magnetic resonance longitudinal relaxation time T1 of the open area, muscle tissue area and closed area of ​​the blood-brain barrier corresponding to time t2. Repeat the above measurement steps, inject m times of contrast agent at different times, perform m groups of magnetic resonance T1 dynamic tests QMRI base(m) and QMRI measure(m), and obtain t m The T1 magnetic resonance longitudinal relaxation time T1 corresponding to the moment. Wherein, the value of m is a positive integer, which is not specifically limited. According to the magnetic resonance T1 spectrum obtained by multiple measurements, the contrast agent concentrations in the open area of ​​the blood-brain barrier, the muscle tissue area, and the closed area of ​​the blood-brain barrier in the target brain area can be obtained. On this basis, the pre-constructed muscle contrast agent concentration attenuation model is fitted and solved according to the muscle contrast agent concentrations corresponding to multiple contrast agent injection moments, and the decay time coefficient of the muscle contrast agent concentration and the muscle jump amplitude of the muscle contrast agent concentration at each contrast agent injection moment can be obtained. Then, according to the open area contrast agent concentrations, the decay time coefficient, and the muscle jump amplitude corresponding to multiple contrast agent injection moments, the pre-constructed open area recovery model is fitted and solved to obtain the recovery time coefficient of the open area of ​​the blood-brain barrier and the open jump amplitude of the open area contrast agent concentration at each contrast agent injection moment. Finally, the recovery time of the open area of ​​the blood-brain barrier, i.e., the closing time, is predicted by combining the closing contrast agent concentration in the closed area of ​​the blood-brain barrier, the recovery time coefficient in the open area of ​​the blood-brain barrier, and the opening jump amplitude of the contrast agent concentration in the open area.

[0118] Optionally, in order to verify the closing time of the open area of ​​the blood-brain barrier, the closed area of ​​the blood-brain barrier is selected as a reference standard for the change in contrast agent concentration when the open area of ​​the blood-brain barrier is closed at different times. When the contrast agent concentration in the open area of ​​the blood-brain barrier is consistent with the contrast agent concentration in the closed area of ​​the blood-brain barrier, it means that the open area of ​​the blood-brain barrier has been closed and has reached a recovery state. Therefore, the recovery time of the open area of ​​the blood-brain barrier can be verified by the closed contrast agent concentration in the closed area of ​​the blood-brain barrier.

[0119] The technical solution of this embodiment is to fit and solve the pre-constructed muscle contrast agent concentration attenuation model according to the muscle contrast agent concentration corresponding to multiple contrast agent injection moments, and obtain the decay time coefficient of the muscle contrast agent concentration and the muscle jump amplitude of the muscle contrast agent concentration at each contrast agent injection moment, so as to fit and solve the pre-constructed muscle contrast agent concentration attenuation model using the data of contrast agent injection at multiple moments, and obtain the muscle jump amplitude of the muscle contrast agent concentration at each injection moment. According to the open area contrast agent concentration, the decay time coefficient, and the muscle jump amplitude corresponding to multiple contrast agent injection moments, the pre-constructed open area recovery model is fitted and solved to obtain the recovery time coefficient of the open area of ​​the blood-brain barrier and the open jump amplitude of the open area contrast agent concentration at each contrast agent injection moment, so as to fit and solve the open area contrast agent concentration, decay time coefficient, and muscle jump amplitude to the pre-constructed open area recovery model, so as to obtain the open jump amplitude of the open area contrast agent concentration at each contrast agent injection moment. The closing time of the open area of ​​the blood-brain barrier is determined based on the closing contrast agent concentration, the opening jump amplitude and the recovery time coefficient, so as to predict the closing time of the open area of ​​the blood-brain barrier according to the closing contrast agent concentration, the opening jump amplitude and the recovery time coefficient obtained by the pre-built model. The problem that the closing time of the blood-brain barrier cannot be predicted in the prior art is solved, and the effect of accurately predicting the closing time of the open area of ​​the blood-brain barrier is achieved.

[0120] Embodiment 3

[0121] Figure 5 This is a schematic diagram of the structure of the blood-brain barrier closing time determination device provided in the third embodiment of the present invention. The blood-brain barrier closing time determination device provided in this embodiment can be implemented by software and / or hardware, and can be configured in a terminal and / or server to implement the blood-brain barrier closing time determination method in the embodiment of the present invention. The device may specifically include: a magnetic resonance spectrum acquisition module 510, a region determination module 520, a magnetic resonance longitudinal relaxation time determination module 530, a contrast agent concentration determination module 540, and a blood-brain barrier closing time determination module 550.

[0122] The magnetic resonance spectrum acquisition module 510 is used to respectively acquire magnetic resonance longitudinal relaxation time spectra corresponding to multiple contrast agent injection moments of the target brain region in the process of opening the blood-brain barrier of the target brain region of the target object by magnetic resonance-guided ultrasound, wherein the magnetic resonance longitudinal relaxation time spectrum corresponding to each of the contrast agent injection moments includes a magnetic resonance longitudinal relaxation time spectrum at a moment before the contrast agent is injected and a magnetic resonance longitudinal relaxation time spectrum at a moment after the contrast agent is injected;

[0123] A region determination module 520, configured to determine a blood-brain barrier open region of the target brain region, a muscle tissue region corresponding to the blood-brain barrier open region, and a blood-brain barrier closed region corresponding to the blood-brain barrier open region;

[0124] The magnetic resonance longitudinal relaxation time determination module 530 is used to determine, for each magnetic resonance longitudinal relaxation time spectrum, a first magnetic resonance longitudinal relaxation time of the open area of ​​the blood-brain barrier, a second magnetic resonance longitudinal relaxation time of the muscle tissue area, and a third magnetic resonance longitudinal relaxation time of the closed area of ​​the blood-brain barrier;

[0125] a contrast agent concentration determination module 540, configured to determine an open area contrast agent concentration of the open area of ​​the blood-brain barrier based on the first magnetic resonance longitudinal relaxation time, determine a muscle contrast agent concentration of the muscle tissue area based on the second magnetic resonance longitudinal relaxation time, and determine a closed contrast agent concentration of the closed area of ​​the blood-brain barrier based on the third magnetic resonance longitudinal relaxation time;

[0126] The blood-brain barrier closing time determination module 550 is used to determine the closing time of the open area of ​​the blood-brain barrier according to the open area contrast agent concentration, the muscle contrast agent concentration and the closed contrast agent concentration corresponding to multiple contrast agent injection moments.

[0127] The above technical solution calculates the contrast agent concentrations of the open area of ​​the blood-brain barrier, the muscle tissue area and the closed area of ​​the blood-brain barrier at each contrast agent moment through the magnetic resonance longitudinal relaxation time spectrum at each contrast agent moment, and then determines the closing time of the open area of ​​the blood-brain barrier, which solves the problem in the prior art that the recovery time of the blood-brain barrier after opening cannot be predicted, and achieves the effect of accurately predicting the closing time of the blood-brain barrier.

[0128] Based on any optional technical solution in the embodiments of the present invention, optionally, the blood-brain barrier closing time determination module specifically includes:

[0129] The muscle area attenuation determination submodule is used to fit and solve the pre-constructed muscle contrast agent concentration attenuation model according to the muscle contrast agent concentrations corresponding to multiple contrast agent injection moments, and obtain the attenuation time coefficient of the muscle contrast agent concentration and the muscle jump amplitude of the muscle contrast agent concentration at each contrast agent injection moment;

[0130] An open area attenuation determination submodule is used to fit and solve a pre-constructed open area recovery model according to the open area contrast agent concentration, the attenuation time coefficient, and the muscle jump amplitude corresponding to multiple contrast agent injection moments, to obtain the recovery time coefficient of the open area of ​​the blood-brain barrier and the open jump amplitude of the contrast agent concentration in the open area at each contrast agent injection moment;

[0131] A closing time determination submodule, for determining the closing time of the open area of ​​the blood-brain barrier based on the closing contrast agent concentration, the opening jump amplitude and the recovery time coefficient;

[0132] Among them, the closed contrast agent concentration is determined based on the closed contrast agent concentration attenuation model; the open area recovery model is constructed based on the muscle contrast agent concentration attenuation model; the muscle contrast agent concentration attenuation model and the closed contrast agent concentration attenuation model are both constructed based on an exponential attenuation function.

[0133] Based on any optional technical solution in the embodiments of the present invention, optionally, the open area recovery model is:

[0134]

[0135] Among them, C f (t) represents the contrast agent concentration in the open area of ​​the blood-brain barrier at time t, Ap represents the jump amplitude of the contrast agent concentration in the open area at each contrast agent injection time, · represents multiplication operation, λ represents the recovery time coefficient of the open area of ​​the blood-brain barrier, * represents convolution operation, u(t) represents the unit input function, b is a constant, bC m (t) represents the vascular contrast agent concentration.

[0136] Based on any optional technical solution in the embodiments of the present invention, optionally, the muscle contrast agent concentration attenuation model is:

[0137] C m (t) = Bp·e -μt *u(t)

[0138] Among them, C m (t) represents the muscle contrast agent concentration in the muscle tissue area at time t, Bp represents the muscle jump amplitude of the muscle contrast agent concentration at each contrast agent injection moment, · represents multiplication operation, μ represents the attenuation time coefficient of the muscle contrast agent concentration, * represents convolution operation, and u(t) represents the unit input function.

[0139] Based on any optional technical solution in the embodiments of the present invention, optionally, the blood-brain barrier closing time determination submodule is used to:

[0140] The closing time of the open area of ​​the blood-brain barrier is determined based on the following formula and the concentration of the closed contrast agent, the open jump amplitude and the recovery time coefficient:

[0141]

[0142] Among them, T c represents the closing time of the open area of ​​the blood-brain barrier, C c (t) is the closed contrast agent concentration of the blood-brain barrier closed area at time t, Indicates that the blood-brain barrier closed area at t = T c The closed contrast agent concentration at the moment, Ap represents the muscle jump amplitude of the contrast agent concentration in the open area at each contrast agent injection moment, · represents multiplication operation, and λ represents the recovery time coefficient of the open area of ​​the blood-brain barrier.

[0143] Based on any optional technical solution in the embodiments of the present invention, optionally, the contrast agent concentration determination module is used to:

[0144] The open area contrast agent concentration of the blood-brain barrier open area is determined based on the following formula and the first magnetic resonance longitudinal relaxation time:

[0145]

[0146] Among them, C f (t) represents the contrast agent concentration in the open area of ​​the blood-brain barrier at time t, R1 represents the relaxation rate of the contrast agent, T 10f represents the first magnetic resonance longitudinal relaxation time of the open area of ​​the blood-brain barrier when no contrast agent is injected, T 1f (t) represents the first magnetic resonance longitudinal relaxation time of the open area of ​​the blood-brain barrier at time t.

[0147] Based on any optional technical solution in the embodiments of the present invention, optionally, the magnetic resonance spectrum acquisition module is used to:

[0148] Based on the variable flip angle magnetic resonance imaging technology, a magnetic resonance longitudinal relaxation time spectrum corresponding to multiple contrast agent injection moments of the target brain area is obtained.

[0149] The above-mentioned device for determining the closing time of the blood-brain barrier can execute the method for determining the closing time of the blood-brain barrier provided by any embodiment of the present invention, and has the corresponding functional modules and beneficial effects of the execution method.

[0150] Embodiment 4

[0151] Figure 6 This is a schematic diagram of the structure of an electronic device provided in Embodiment 4 of the present invention. Figure 6 A block diagram of an exemplary electronic device 12 suitable for use in implementing embodiments of the present invention is shown. Figure 6 The electronic device 12 shown is only an example and should not bring any limitation to the functions and scope of use of the embodiments of the present invention.

[0152] like Figure 6 As shown, the electronic device 12 is in the form of a general purpose computing device. The components of the electronic device 12 may include, but are not limited to: one or more processors or processing units 16, a system memory 28, and a bus 18 that connects various system components (including the system memory 28 and the processing unit 16).

[0153] Bus 18 represents one or more of several types of bus structures, including a memory bus or memory controller, a peripheral bus, an accelerated graphics port, a processor or a local bus using any of a variety of bus architectures. By way of example, these architectures include, but are not limited to, an Industry Standard Architecture (ISA) bus, a Micro Channel Architecture (MAC) bus, an Enhanced ISA bus, a Video Electronics Standards Association (VESA) local bus, and a Peripheral Component Interconnect (PCI) bus.

[0154] The electronic device 12 typically includes a variety of computer system readable media. These media can be any available media that can be accessed by the electronic device 12, including volatile and non-volatile media, removable and non-removable media.

[0155] The system memory 28 may include computer system readable media in the form of volatile memory, such as random access memory (RAM) 30 and / or cache memory 32. The electronic device 12 may further include other removable / non-removable, volatile / non-volatile computer system storage media. By way of example only, the storage system 34 may be used to read and write non-removable, non-volatile magnetic media ( Figure 6 not shown, usually called a "hard drive"). Although Figure 6 Not shown in the figure, a disk drive for reading and writing to a removable non-volatile disk (e.g., a "floppy disk"), and an optical disk drive for reading and writing to a removable non-volatile optical disk (e.g., a CD-ROM, a DVD-ROM, or other optical media) may be provided. In these cases, each drive may be connected to the bus 18 via one or more data medium interfaces. The system memory 28 may include at least one program product having a set (e.g., at least one) of program modules that are configured to perform the functions of the embodiments of the present invention.

[0156] A program / utility 40 having a set (at least one) of program modules 42 may be stored, for example, in system memory 28, such program modules 42 including, but not limited to, an operating system, one or more application programs, other program modules, and program data, each of which or some combination may include an implementation of a network environment. Program modules 42 generally perform the functions and / or methods of the embodiments described herein.

[0157] The electronic device 12 may also communicate with one or more external devices 14 (e.g., keyboards, pointing devices, displays 24, etc.), may communicate with one or more devices that enable a user to interact with the electronic device 12, and / or may communicate with any device that enables the electronic device 12 to communicate with one or more other computing devices (e.g., network cards, modems, etc.). Such communication may be performed via an input / output (I / O) interface 22. Furthermore, the electronic device 12 may also communicate with one or more networks (e.g., local area networks (LANs), wide area networks (WANs), and / or public networks, such as the Internet) via a network adapter 20. Figure 6 As shown, the network adapter 20 communicates with other modules of the electronic device 12 via the bus 18. It should be understood that although Figure 6 Not shown, other hardware and / or software modules may be used in conjunction with the electronic device 12, including but not limited to: microcode, device drivers, redundant processing units, external disk drive arrays, RAID systems, tape drives, and data backup storage systems.

[0158] The processing unit 16 executes various functional applications and data processing by running the programs stored in the system memory 28, such as implementing a method for determining the closing time of the blood-brain barrier provided in the embodiment of the present invention.

[0159] Embodiment 5

[0160] Embodiment 5 of the present invention further provides a storage medium comprising computer executable instructions, wherein the computer executable instructions are used to execute a method for determining blood-brain barrier closing time when executed by a computer processor, the method comprising:

[0161] In the process of opening the blood-brain barrier of the target brain area of ​​the target object through magnetic resonance-guided ultrasound, magnetic resonance longitudinal relaxation time maps of the target brain area corresponding to multiple contrast agent injection moments are respectively obtained, wherein the magnetic resonance longitudinal relaxation time map corresponding to each of the contrast agent injection moments includes the magnetic resonance longitudinal relaxation time map at the moment before the contrast agent is injected and the magnetic resonance longitudinal relaxation time map at the moment after the contrast agent is injected; the blood-brain barrier opening area of ​​the target brain area, the muscle tissue area corresponding to the blood-brain barrier opening area, and the blood-brain barrier closed area corresponding to the blood-brain barrier opening area are determined; for each magnetic resonance longitudinal relaxation time map, the blood-brain barrier opening area is respectively determined. a first magnetic resonance longitudinal relaxation time of the barrier open area, a second magnetic resonance longitudinal relaxation time of the muscle tissue area, and a third magnetic resonance longitudinal relaxation time of the blood-brain barrier closed area; determining the open area contrast agent concentration of the blood-brain barrier open area based on the first magnetic resonance longitudinal relaxation time, determining the muscle contrast agent concentration of the muscle tissue area based on the second magnetic resonance longitudinal relaxation time, and determining the closed contrast agent concentration of the blood-brain barrier closed area based on the third magnetic resonance longitudinal relaxation time; determining the closing time of the blood-brain barrier open area according to the open area contrast agent concentration, the muscle contrast agent concentration, and the closed contrast agent concentration corresponding to multiple contrast agent injection moments.

[0162] The computer storage medium of the embodiment of the present invention can adopt any combination of one or more computer-readable media. The computer-readable medium can be a computer-readable signal medium or a computer-readable storage medium. The computer-readable storage medium can be, for example, but not limited to, an electrical, magnetic, optical, electromagnetic, infrared, or semiconductor system, device or device, or any combination of the above. More specific examples (non-exhaustive list) of computer-readable storage media include: an electrical connection with one or more wires, a portable computer disk, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or flash memory), an optical fiber, a portable compact disk read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the above. In this document, a computer-readable storage medium can be any tangible medium containing or storing a program, which can be used by an instruction execution system, device or device or used in combination with it.

[0163] Computer-readable signal media may include data signals propagated in baseband or as part of a carrier wave, which carry computer-readable program code. Such propagated data signals may take a variety of forms, including but not limited to electromagnetic signals, optical signals, or any suitable combination of the above. Computer-readable signal media may also be any computer-readable medium other than a computer-readable storage medium, which may send, propagate, or transmit a program for use by or in conjunction with an instruction execution system, apparatus, or device.

[0164] Program code embodied on a computer readable medium may be transmitted using any appropriate medium, including but not limited to wireless, wireline, optical fiber cable, RF, etc., or any suitable combination of the foregoing.

[0165] Computer program code for performing the operation of embodiments of the present invention may be written in one or more programming languages ​​or a combination thereof, including object-oriented programming languages, such as Java, Smalltalk, C++, and conventional procedural programming languages, such as "C" or similar programming languages. The program code may be executed entirely on a user's computer, partially on a user's computer, as an independent software package, partially on a user's computer and partially on a remote computer, or entirely on a remote computer or server. In the case of a remote computer, the remote computer may be connected to the user's computer via any type of network, including a local area network (LAN) or a wide area network (WAN), or may be connected to an external computer (e.g., via the Internet using an Internet service provider).

[0166] Note that the above are only preferred embodiments of the present invention and the technical principles used. Those skilled in the art will understand that the present invention is not limited to the specific embodiments described herein, and that various obvious changes, readjustments and substitutions can be made by those skilled in the art without departing from the scope of protection of the present invention. Therefore, although the present invention has been described in more detail through the above embodiments, the present invention is not limited to the above embodiments, and may include more other equivalent embodiments without departing from the concept of the present invention, and the scope of the present invention is determined by the scope of the appended claims.

Claims

1. A method for determining blood-brain barrier closing time, characterized in that: include: In the process of opening the blood-brain barrier of the target brain region of the target object by magnetic resonance-guided ultrasound, respectively obtaining magnetic resonance longitudinal relaxation time maps of the target brain region corresponding to multiple contrast agent injection moments, wherein the magnetic resonance longitudinal relaxation time map corresponding to each of the contrast agent injection moments includes a magnetic resonance longitudinal relaxation time map at a moment before the contrast agent is injected and a magnetic resonance longitudinal relaxation time map at a moment after the contrast agent is injected; Determining a blood-brain barrier open area of ​​the target brain region, a muscle tissue area corresponding to the blood-brain barrier open area, and a blood-brain barrier closed area corresponding to the blood-brain barrier open area; For each magnetic resonance longitudinal relaxation time spectrum, respectively determining a first magnetic resonance longitudinal relaxation time of the open region of the blood-brain barrier, a second magnetic resonance longitudinal relaxation time of the muscle tissue region, and a third magnetic resonance longitudinal relaxation time of the closed region of the blood-brain barrier; Determine the contrast agent concentration of the open area of ​​the blood-brain barrier based on the first magnetic resonance longitudinal relaxation time, determine the muscle contrast agent concentration of the muscle tissue area based on the second magnetic resonance longitudinal relaxation time, and determine the closed contrast agent concentration of the blood-brain barrier closed area based on the third magnetic resonance longitudinal relaxation time; The closing time of the open area of ​​the blood-brain barrier is determined according to the open area contrast agent concentration, the muscle contrast agent concentration and the closed contrast agent concentration corresponding to multiple contrast agent injection moments.

2. The method according to claim 1, characterized in that The step of determining the closing time of the open area of ​​the blood-brain barrier according to the open area contrast agent concentration, the muscle contrast agent concentration, and the closed contrast agent concentration comprises: Fitting and solving a pre-constructed muscle contrast agent concentration attenuation model according to the muscle contrast agent concentrations corresponding to multiple contrast agent injection moments, to obtain the attenuation time coefficient of the muscle contrast agent concentration and the muscle jump amplitude of the muscle contrast agent concentration at each contrast agent injection moment; According to the open area contrast agent concentration, the decay time coefficient, and the muscle jump amplitude corresponding to multiple contrast agent injection moments, a pre-constructed open area recovery model is fitted and solved to obtain the recovery time coefficient of the open area of ​​the blood-brain barrier and the open jump amplitude of the contrast agent concentration in the open area at each contrast agent injection moment; Determining the closing time of the open area of ​​the blood-brain barrier based on the closing contrast agent concentration, the opening jump amplitude and the recovery time coefficient; Among them, the closed contrast agent concentration is determined based on the closed contrast agent concentration attenuation model; the open area recovery model is constructed based on the muscle contrast agent concentration attenuation model; the muscle contrast agent concentration attenuation model and the closed contrast agent concentration attenuation model are both constructed based on an exponential attenuation function.

3. The method according to claim 2, characterized in that The open area recovery model is: Among them, C f (t) represents the contrast agent concentration in the open area of ​​the blood-brain barrier at time t, Ap represents the muscle jump amplitude of the contrast agent concentration in the open area at each contrast agent injection time, · represents multiplication operation, λ represents the recovery time coefficient of the open area of ​​the blood-brain barrier, * represents convolution operation, u(t) represents the unit input function, b is a constant, bC m (t) represents the vascular contrast agent concentration.

4. The method according to claim 2, characterized in that: The muscle contrast agent concentration attenuation model is: C m (t)=Bp·e -μt *u(t) Among them, C m (t) represents the muscle contrast agent concentration in the muscle tissue area at time t, Bp represents the muscle jump amplitude of the muscle contrast agent concentration at each contrast agent injection moment, · represents multiplication operation, μ represents the attenuation time coefficient of the muscle contrast agent concentration, * represents convolution operation, and u(t) represents the unit input function.

5. The method according to claim 2, characterized in that: Determining the closing time of the open area of ​​the blood-brain barrier based on the closing contrast agent concentration, the opening jump amplitude and the recovery time coefficient includes: The closing time of the open area of ​​the blood-brain barrier is determined based on the following formula and the concentration of the closed contrast agent, the open jump amplitude and the recovery time coefficient: Among them, T c represents the closing time of the open area of ​​the blood-brain barrier, C c (t) is the closed contrast agent concentration in the closed area of ​​the blood-brain barrier at time t, Indicates that the blood-brain barrier closed area at t = T c The closed contrast agent concentration at the moment, Ap represents the muscle jump amplitude of the contrast agent concentration in the open area at each contrast agent injection moment, · represents multiplication operation, and λ represents the recovery time coefficient of the open area of ​​the blood-brain barrier.

6. The method according to claim 1, characterized in that The step of determining the open area contrast agent concentration of the blood-brain barrier open area based on the first magnetic resonance longitudinal relaxation time comprises: The open area contrast agent concentration of the blood-brain barrier open area is determined based on the following formula and the first magnetic resonance longitudinal relaxation time: Among them, C f (t) represents the contrast agent concentration in the open area of ​​the blood-brain barrier at time t, R1 represents the relaxation rate of the contrast agent, T 10f represents the first magnetic resonance longitudinal relaxation time of the open area of ​​the blood-brain barrier when no contrast agent is injected, T 1f (t) represents the first magnetic resonance longitudinal relaxation time of the open area of ​​the blood-brain barrier at time t.

7. The method according to claim 1, characterized in that The step of respectively acquiring magnetic resonance longitudinal relaxation time maps of the target brain region corresponding to a plurality of contrast agent injection moments comprises: Based on the variable flip angle magnetic resonance imaging technology, a magnetic resonance longitudinal relaxation time spectrum corresponding to multiple contrast agent injection moments of the target brain area is obtained.

8. A device for determining blood-brain barrier closing time, characterized in that: include: A magnetic resonance spectrum acquisition module is used to respectively acquire magnetic resonance longitudinal relaxation time spectra corresponding to multiple contrast agent injection moments of the target brain region in the process of opening the blood-brain barrier of the target brain region of the target object by magnetic resonance-guided ultrasound, wherein the magnetic resonance longitudinal relaxation time spectrum corresponding to each of the contrast agent injection moments includes a magnetic resonance longitudinal relaxation time spectrum at a moment before the contrast agent is injected and a magnetic resonance longitudinal relaxation time spectrum at a moment after the contrast agent is injected; A region determination module, used to determine the blood-brain barrier open region of the target brain region, the muscle tissue region corresponding to the blood-brain barrier open region, and the blood-brain barrier closed region corresponding to the blood-brain barrier open region; A magnetic resonance longitudinal relaxation time determination module, for determining, for each magnetic resonance longitudinal relaxation time spectrum, a first magnetic resonance longitudinal relaxation time of the open region of the blood-brain barrier, a second magnetic resonance longitudinal relaxation time of the muscle tissue region, and a third magnetic resonance longitudinal relaxation time of the closed region of the blood-brain barrier; a contrast agent concentration determination module, configured to determine an open area contrast agent concentration of the open area of ​​the blood-brain barrier based on the first magnetic resonance longitudinal relaxation time, determine a muscle contrast agent concentration of the muscle tissue area based on the second magnetic resonance longitudinal relaxation time, and determine a closed contrast agent concentration of the closed area of ​​the blood-brain barrier based on the third magnetic resonance longitudinal relaxation time; The blood-brain barrier closing time determination module is used to determine the closing time of the open area of ​​the blood-brain barrier according to the open area contrast agent concentration, the muscle contrast agent concentration and the closed contrast agent concentration corresponding to multiple contrast agent injection moments.

9. An electronic device, characterized in that: The electronic device comprises: one or more processors; a storage device for storing one or more programs, When the one or more programs are executed by the one or more processors, the one or more processors implement the method for determining the blood-brain barrier closing time as described in any one of claims 1 to 7.

10. A computer-readable storage medium having a computer program stored thereon, characterized in that: When the program is executed by a processor, the method for determining the blood-brain barrier closing time as described in any one of claims 1 to 7 is implemented.

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