CN111751770A - Method for quantitatively measuring exchange speed of water molecules inside and outside blood vessels by means of non-magnetic resonance contrast agent - Google Patents

Method for quantitatively measuring exchange speed of water molecules inside and outside blood vessels by means of non-magnetic resonance contrast agent Download PDF

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CN111751770A
CN111751770A CN202010537870.8A CN202010537870A CN111751770A CN 111751770 A CN111751770 A CN 111751770A CN 202010537870 A CN202010537870 A CN 202010537870A CN 111751770 A CN111751770 A CN 111751770A
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白瑞良
李昭青
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Zhejiang University ZJU
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Abstract

The invention discloses a method for quantitatively measuring the water exchange speed inside and outside a blood vessel, which is not depended on a magnetic resonance contrast agent, and comprises the following steps: acquiring images based on a two-dimensional diffusion exchange DEXSY exchange filtering imaging FEXI magnetic resonance imaging sequence; calculating the significant exchange rate AXR, the significant diffusion coefficient ADC and the filtering coefficient sigma of each pixel point on the image according to the acquired image; collecting a diffusion weighted magnetic resonance image of a multiple diffusion weighted intensity b value; obtaining the blood vessel density f of each pixel point on the image by fitting according to the collected multi-b value diffusion weighted magnetic resonance imageIVIM(ii) a According to the significant exchange rate AXR and the vascular density fIVIMCorrecting the exchange rate of water molecules inside and outside the blood vessel to obtain the outflow rate k of the water molecules inside the blood vesselbo. The method provided by the invention can realize the specific detection of the water molecule exchange process inside and outside the blood vessel, analyze the apparent water molecule exchange rate inside and outside the blood vessel and obtain the standardAnd (4) determining the exchange rate constant of water molecules inside and outside the blood vessel.

Description

Method for quantitatively measuring exchange speed of water molecules inside and outside blood vessels by means of non-magnetic resonance contrast agent
Technical Field
The invention relates to the technical field of magnetic resonance imaging, in particular to a magnetic resonance imaging method for measuring the exchange speed of water molecules inside and outside a blood vessel.
Background
The exchange rate of water molecules inside and outside blood vessels can reflect biological information (Dickie et al, 2019) such as vascular permeability, neurovascular coupling and the like (Rooney et al, 2015), and is a potential medical imaging technology. The measurement of the exchange rate of water molecules inside and outside blood vessels can only depend on the magnetic resonance imaging technology at present, and at present, two main methods exist: (1) a magnetic resonance contrast agent based method. The method realizes the measurement of the exchange rate of water molecules inside and outside the blood vessel by injecting a magnetic resonance contrast agent (such as Chinese patent application with the publication number of CN 110391016A) into the blood vessel (vein) so as to mark the water molecules inside the blood vessel. The main drawback of this method is the need to use magnetic resonance contrast agents, which on the one hand increase the economic burden on the patient and on the other hand are not suitable for people with impaired renal function (Beam AS et al, 2017). (2) Magnetic resonance methods based on arterial spin labeling. The method realizes the measurement of the exchange of water molecules inside and outside the blood vessel by marking the arterial signals, but the method depends on the effectiveness of marking the arterial signals, and the imaging and signal analysis are complex, so the robustness of the method applied in organisms at present is poor.
Therefore, how to realize quantitative measurement of the intra-and-extravascular water molecule exchange speed which is not depended on by the magnetic resonance contrast agent and has better robustness is a problem which needs to be solved by the technical personnel in the field at present.
Disclosure of Invention
In view of the above, the present invention provides a method for quantitative measurement of the exchange velocity of water molecules inside and outside blood vessels without depending on a magnetic resonance contrast agent. The method provided by the invention can realize the specific detection of the water molecule exchange process inside and outside the blood vessel, analyze the apparent water molecule exchange rate inside and outside the blood vessel and obtain the accurate water molecule exchange rate constant inside and outside the blood vessel.
In order to achieve the purpose, the invention adopts the following technical scheme:
(1) acquiring images based on a two-dimensional diffusion exchange DEXSY exchange filtering imaging FEXI magnetic resonance imaging sequence;
(2) calculating the significant exchange rate AXR, the significant diffusion coefficient ADC and the filtering coefficient sigma of each pixel point on the image according to the image acquired in the step (1);
(3) collecting a diffusion weighted magnetic resonance image of a multiple diffusion weighted intensity b value; (ii) a
(4) Obtaining the diffusion weighted magnetic resonance image according to the multiple b values acquired in the step (3) through fittingBlood vessel density f of each pixel point on the imageIVIM；
(5) According to the significant exchange rate AXR in step (2) and the blood vessel density f in step (4)IVIMCorrecting the exchange rate of water molecules inside and outside the blood vessel to obtain the outflow rate k of the water molecules inside the blood vesselbo。
The method provided by the invention comprises three parts, namely magnetic resonance imaging data acquisition (steps 1 and 3), a data analysis method (step 2) and an error correction method (steps 4 and 5).
In step (1), the FEXI magnetic resonance imaging sequence comprises a filtering module, an exchange module and a detection module; a single PGSE sequence in both the filtering module and the detection module; setting an appropriate diffusion weighting b value in the filtering module; setting a switching time t in a switching modulem(ii) a Detecting the passage of the switching time t in the detection modulemThe latter magnetic resonance signals.
The filtering module can eliminate the influence of the movement of water molecules in the blood vessel along with the blood flow on the magnetic resonance signal by setting a proper diffusion weighting b value; setting exchange time tm in the exchange module, wherein water molecules inside and outside the blood vessel are exchanged within the exchange time, so that the exchange of the magnetization vectors of the water molecules is caused; the detection module can detect the passing of the exchange time tmThe latter magnetic resonance signals.
In step (1), the FEXI magnetic resonance imaging sequence acquires two images: the filter module is set to non-0 diffusion weighting, i.e. b, when the first image is acquiredfIf more than 0, the exchange module sets the exchange time tmThe measurement is carried out, the diffusion weighting of the detection module comprises two b values set as b1And b2Separately, magnetic resonance signals S (t) are obtainedm，b1) And S (t)m，b2) (ii) a When the second image is collected, the filtering module is set as 0 diffusion weighting, the exchange module is set as the shortest exchange time, the diffusion weighting of the detection module comprises two b values, the setting is the same as the first image collection, and is b1And b2Separately obtaining magnetic resonance signals S0(b1)，S0(b2)。
Preferably, the shortest echo Time (TE) in the filtering module and the detecting module can improve the image signal-to-noise ratio.
Preferably, b in the non-0 diffusion weighting in the filtering module during the first image acquisitionfIs 50s/mm2-400s/mm2。
Preferably, the switching module switches the time tmThe shortest switching time is between 1000 ms.
Preferably, the switching module is configured to set a plurality of (> ═ 2) switching times for performing a plurality of measurements.
Preferably, b in the detection module1Not more than 10s/mm2，b2Is 50s/mm2-400s/mm2。
Preferably, in step (2), the image may be pre-processed (eddy current, motion correction, etc.).
In step (2), AXR, ADC and σ are passed through t, which is knownmAnd a difference calculated from tmSignificant diffusion coefficient of lower ADC' (t)m) For formula ADC' (t)m)＝ADC(1-σexp(-tmAXR)) is obtained by fitting with a least squares sum method;
ADC′(tm) Is obtained by the formula
Figure BDA0002537693100000031
Calculated, wherein S (t)m，b1) And S (t)m，b2) The magnetic resonance signal is acquired by two diffusion weighted images of the detection module when the first image is acquired; in which the significant diffusion coefficient ADC' in equilibrium (t)mInfinity) is by the formula
Figure BDA0002537693100000041
Get, by default, infinite exchange time, i.e. tm＝∞。
Preferably, in step (3), the value of b is 25s/mm2Step size is from 0s/mm2To 200s/mm2At 50s/mm2In steps of 250s/mm2To 500s/mm2Bag for containingIncluding 15 b values.
In step (4), fIVIMIs obtained by adding f to the formula S (b)/S (b) ═ 0IVIMexp(-bD*)+(1-fIVIM) exp (-bD) is obtained by adopting a step-by-step fitting mode, wherein S (b) is a signal obtained by collecting a diffusion weighted magnetic resonance image with multiple b values, D is an apparent diffusion coefficient of water molecules in blood vessels, and D is an apparent diffusion coefficient of water molecules in tissues.
In step (5), according to formula kbo＝AXR(1-fIVIM) Obtaining the final outflow rate k of the water molecules in the blood vesselbo。
Preferably, in step (5), the pair f may also be different according to the blood and tissue T2IVIMAnd (6) performing correction.
In order to more clearly explain the technical scheme of the invention, the following description is made:
the method provided by the invention does not need to use a magnetic resonance contrast agent, and the magnetic resonance sequence of the invention adopts diffusion-based exchange weighted imaging (FEXI) and realizes the specific detection of the exchange process of water molecules inside and outside the blood vessel by optimizing the diffusion weighted parameters of the filtering module and the detecting module.
Intravascular water molecules generally exist in two flow states: (1) the flow of blood from the intravascular flow to the extravascular (2) blood vessel drives the water molecules in the blood vessel to flow along the blood vessel. The flow of water molecules in both cases brings about a change in the dispersive magnetic resonance signal. The invention aims to measure the exchange condition of water molecules in blood vessels and water molecules outside the blood vessels. To achieve this, the invention sets the appropriate diffusion weighting strength, i.e. b, in the filter module of the FEXI sequencefValue to filter out the magnetic resonance signals of the intravascular water molecules and to set different exchange times t in the exchange modulemDetecting the passing t at the detecting modulemThe magnetic resonance signals after the exchange time. And then calculating the significant diffusion coefficient ADC' under different exchange times by using the FEXI magnetic resonance signals under different exchange times. And fitting the ADC' under different exchange times by adopting a least squares sum method to obtain the significant exchange rate AXR of the tissue. Using multiple b-value diffusion plusEstimation of tissue vascular density f by magnetic resonance imagingIVIMThe blood vessel density parameter is utilized to correct the AXR, and finally the outflow rate k of water molecules in the blood vessel is obtainedbo。
Drawings
FIG. 1 is a schematic FEXI sequence;
FIG. 2 is a flowchart of the operation of an embodiment;
FIG. 3 shows the fitted significant diffusion coefficients at different exchange times in the FEXI sequence;
figure 4 shows the fitted vascular density, significant exchange rate, significant diffusion coefficient and filtration coefficient of the invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the technical solutions of the present invention will be described clearly and completely with reference to the accompanying drawings.
FEXI can be used to measure the rate of exchange of water molecules between two components with different diffusion coefficients. The FEXI sequence used in the present invention is shown in fig. 1. The sequence comprises three modules, namely a filtering module (Filterblock), a switching module (Mixing time) and a Detection module (Detection block). In both the filtration module and the detection module is a single PGSE (pulse Gradient Spin echo) sequence.
As a specific implementation example, the magnetic resonance imaging method for measuring the exchange rate of water molecules inside and outside blood vessels provided by the present invention is applied to the brain of an adult healthy subject, and the operation flowchart is shown in fig. 2, which specifically includes the following steps:
the method comprises the following steps: the adult healthy subject is placed in a 3T magnetic resonance imaging system, and the image acquisition of the head is carried out by taking the center of the head as a scanning central point. The present example of implementation acquires magnetic resonance data of a total of 7 adult healthy subjects.
Step two, setting FEXI sequence and setting the resolution as 3 × 3mm2The layer thickness was 5mm, and 20 layers in total were collected. Wherein the diffusion weight of the filter module should be set to 250s/mm2The diffusion weighting of the detection module should be set to 0s/mm2(b1) And 250s/mm2(b2). Exchange module deviceSetting 3 different exchange times (t)m) Multiple measurements were made at 25ms, 200ms, and 400ms, respectively. Echo time TE of a filter modulefThe echo time TE of the acquisition module is set to 26ms, 37ms, and the time from the third 90 ° pulse in fig. 1 to the start of the next sequence repetition is 2500ms, and the imaging result of the FEXI sequence is obtained.
Step three: change the diffusion weighting of the filter module in FEXI sequence to 0s/mm2And setting the exchange time of the exchange module as the shortest exchange time, keeping the other parameters unchanged, and acquiring the FEXI data again.
Setting a single PGSE sequence, and acquiring a multi-b-value gradient weighted echo magnetic resonance image, wherein the resolution is set to be 3 × 3mm2The layer thickness was 5mm, and 20 layers in total were collected. Wherein the echo time TE is set to 42ms, the repetition time TR is set to 2500ms, the diffusion weighting is set to 25s/mm2Step size is from 0s/mm2To 200s/mm2At 50s/mm2In steps of 250s/mm2To 500s/mm2A total of 15 values are included.
Step five: using the data collected in the second and third steps according to a formula
Figure BDA0002537693100000061
Figure BDA0002537693100000062
Calculate the difference tmSignificant diffusion coefficient (ADC' (t)m) Wherein S (t)m，b1) And S (t)m，b2) Is the magnetic resonance signal acquired at the detection module from the two diffusion weighted images. Further to the formula ADC' (t)m)＝ADC(1-σexp(-tmAXR)) is fitted by a least squares sum method to obtain a significant exchange rate (AXR), a significant diffusion coefficient (ADC) and a filter coefficient (σ) of each pixel point on the image.
Step six: using the data collected in step four to obtain the formula S (b)/S (b is 0) fIVIMexp(-bD*)+(1-fIVIM) exp (-bD) is a step-fitting approach (Iima et al, 2015), where S (b) is a multi-b-value gradient weighted echo magnetThe signal obtained under the resonance image acquisition can be fitted to obtain the blood vessel density f of each pixel point on the imageIVIM。
Step seven: blood vessel density f fitted by step sixIVIMAnd the significant exchange rate AXR obtained in step five is according to the formula kbo＝AXR(1-fIVIM) Correcting the exchange rate of water molecules inside and outside the blood vessel to finally obtain the outflow rate k of the water molecules in the blood vesselbo。
To demonstrate the effect of the present invention in measuring the exchange rate of water molecules inside and outside blood vessels, the following will illustrate the experimental results of this embodiment with reference to the accompanying drawings:
taking the result of a single-layer image of the cross section of the brain as an example, fig. 3 shows the different switching times t obtained in step five of this embodimentmSignificant diffusion coefficient of (ADC') (t)m)). Fig. 4 shows the significant exchange rate (AXR), the significant diffusion coefficient (ADC), the filter coefficient (σ) and the vessel density (f) fitted in step five and step six of this embodimentIVIM)。
The addition of the following optional steps allows for separate measurements of the outflow rate of intravascular water molecules in grey and white matter of the brain, as well as measurements of the outflow rate of intravascular water molecules in different brain regions of the brain. The optional steps are as follows:
step one, setting an MP2RAGE sequence with the resolution of 1 × 1 × 1.2mm3The echo time is set to 2.76ms, the repetition time is set to 5000ms, the two inversion angles are set to 4 degrees and 5 degrees respectively, and the inversion recovery time is 700ms and 2500ms respectively, so that the structural image of the brain is obtained.
Setting diffusion tensor magnetic resonance imaging (DTI) parameters and setting the resolution as 3 × 3mm2The layer thickness was 5mm, and 20 layers in total were collected. The echo time is set to 47ms and the repetition time is set to 2500 ms. Repeatedly collecting for 2 times, and diffusion weighting to 0s/mm2The image of (2). A single acquisition included a diffusion weighting of 1000s/mm for 20 directions2The image of (2).
Step three, registering the structural image acquired in the step one with an MNI152 template and a J ü lich human brain atlas, and dividing the structural image into 121 brain region. Further the diffusion weighting acquired by the structure image and FEXI sequence is 0s/mm2The re-registration of the images of (a) results in brain partitions on the FEXI data space. Using the ADC, σ, AXR, f of each pixel point on the image obtained in the above steps five and six of the specific embodimentIVIMCalculating ADC, sigma, AXR, f corresponding to 86 brain regionsIVIM. Of which 35 brain regions were not acquired with the magnetic resonance signals of more than 20% of the regions removed.
Step four: and (3) performing nonlinear DTI model fitting on the diffusion tensor imaging data obtained in the step three by using TORTOISE software, and obtaining a partial anisotropy index (FA) and an average diffusivity (MD) of each pixel point of the image.
Step five: and (4) performing tissue segmentation on the structural image acquired in the step one by using a FAST algorithm in FSL software to obtain a probability distribution map of white matter and gray matter. Wherein the probability is 0.5 to 1.0, the FA is 0.35 to 0.99 and the MD is 0.01-1.0 μm2The pixels in/ms are considered as white matter parts. Wherein the probability is 0.5 to 1.0, FA is 0.02 to 0.15 and MD is 0.5-1.3 μm2The pixels in/ms are considered to be gray matter parts. Further, ADC, sigma, AXR, f of all pixel points in gray matter and white matter partsIVIMAs the final ADC, sigma, AXR, f of the gray and white matter fractions, respectivelyIVIM。
The above-mentioned embodiments are intended to illustrate the technical solutions and advantages of the present invention, and it should be understood that the above-mentioned embodiments are only the most preferred embodiments of the present invention, and are not intended to limit the present invention, and any modifications, additions, equivalents, etc. made within the scope of the principles of the present invention should be included in the scope of the present invention.

Claims (10)

1. A method for non-magnetic resonance contrast agent dependent quantitative measurement of the exchange velocity of water molecules inside and outside blood vessels, the method comprising:
(1) acquiring images based on a two-dimensional diffusion exchange DEXSY exchange filtering imaging FEXI magnetic resonance imaging sequence;
(2) calculating the significant exchange rate AXR, the significant diffusion coefficient ADC and the filtering coefficient sigma of each pixel point on the image according to the image acquired in the step (1);
(3) collecting a diffusion weighted magnetic resonance image of a multiple diffusion weighted intensity b value;
(4) obtaining the blood vessel density f of each pixel point on the image by fitting according to the multi-b value diffusion weighted magnetic resonance image acquired in the step (3)IVIM；
(5) According to the significant exchange rate AXR in step (2) and the blood vessel density f in step (4)IVIMCorrecting the exchange rate of water molecules inside and outside the blood vessel to obtain the outflow rate k of the water molecules inside the blood vesselbo。
2. The non-magnetic resonance contrast agent dependent quantitative measurement method of intravascular and extravascular water molecule exchange velocity of claim 1, wherein in step (1), the FEXI magnetic resonance imaging sequence includes a filtering module, an exchange module and a detection module; a single PGSE sequence in both the filtering module and the detection module; setting an appropriate diffusion weighting b value in the filtering module; setting a switching time t in a switching modulem(ii) a Detecting the passage of the switching time t in the detection modulemThe latter magnetic resonance signals.
3. The non-magnetic resonance contrast agent-dependent quantitative measurement method of the intravascular and extravascular water molecule exchange velocity of claim 2, wherein in step (1), a FEXI magnetic resonance imaging sequence acquires two images: the filter module is set to a non-0 diffusion weighting b when the first image is acquiredfThe switching module sets a switching time tmThe measurement is carried out, the diffusion weighting of the detection module comprises two b values set as b1And b2Separately, magnetic resonance signals S (t) are obtainedm,b1)，S(tm,b2) (ii) a When the second image is collected, the filtering module is set as 0 diffusion weighting, the exchange module is set as the shortest exchange time, the diffusion weighting of the detection module comprises two b values, the setting is the same as the first image collection, and is b1And b2Is divided intoObtaining magnetic resonance signals S0(b1)，S0(b2)。
4. A method as claimed in claim 3, wherein the first image is acquired with a non-0 diffusion weighted b in the filter modulefThe value is 50s/mm2-400s/mm2。
5. A method for non-magnetic resonance contrast agent dependent quantitative measurement of the exchange velocity of water molecules inside and outside blood vessels according to claim 3, characterized in that the exchange time t of the exchange module at the time of the first image acquisitionmThe shortest switching time is between 1000 ms.
6. A method for non-magnetic resonance contrast agent dependent quantitative measurement of the exchange velocity of water molecules inside and outside blood vessels according to claim 3, characterized in that when the first image is acquired, a plurality of exchange times are set in the exchange module for a plurality of measurements.
7. The method for non-magnetic resonance contrast agent-dependent quantitative measurement of intravascular and extravascular water molecule exchange velocity of claim 3, wherein b is the detection module1Not more than 10s/mm2，b2Is 50s/mm2-400s/mm2。
8. The non-magnetic resonance contrast agent-dependent quantitative measurement method of intravascular and extravascular water molecule exchange velocity of claim 3, wherein in step (2), AXR, ADC and σ are determined by tmAnd a difference calculated from tmSignificant diffusion coefficient of lower ADC' (t)m) For formula ADC' (t)m)＝ADC(1-σexp(-tmAXR)) is obtained by fitting with a least squares sum method;
ADC′(tm) Is obtained by the formula
Figure FDA0002537693090000021
Calculated, wherein S (t)m,b1) And S (t)m,B2) The magnetic resonance signal is acquired by two diffusion weighted images of the detection module when the first image is acquired; in which the significant diffusion coefficient ADC' in equilibrium (t)mInfinity) is by the formula
Figure FDA0002537693090000022
Get, by default, infinite exchange time, i.e. tm＝∞。
9. The method for non-magnetic resonance contrast agent-dependent quantitative measurement of the intravascular and extravascular water molecule exchange velocity according to claim 1, wherein in step (4), fIVIMIs obtained by adding f to the formula S (b)/S (b) ═ 0IVIMexp(-bD*)+(1-fIVIM) exp (-bD) is obtained by adopting a step-by-step fitting mode, wherein S (b) is a signal obtained by collecting a diffusion weighted magnetic resonance image with multiple b values, D is an apparent diffusion coefficient of water molecules in blood vessels, and D is an apparent diffusion coefficient of water molecules in tissues.
10. The method for non-magnetic resonance contrast agent-dependent quantitative measurement of intravascular and extravascular water molecule exchange velocity according to claim 1, wherein in step (5), according to formula kbo＝AXR(1-fIVIM) Obtaining the final outflow rate k of the water molecules in the blood vesselbo。
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113406546A (en) * 2021-05-06 2021-09-17 华南理工大学 Anti-eddy-current-effect transmembrane water exchange magnetic resonance imaging sequence design method
CN114155225A (en) * 2021-12-07 2022-03-08 浙江大学 Method for quantitatively measuring exchange rate of water molecules inside and outside myelin sheaths of white matter

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
RUILIANG BAI ETC: "《"Feasibility of filter-exchange imaging (FEXI) in measuring different exchange processes in human brain"》", 《NEUROIMAGE》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113406546A (en) * 2021-05-06 2021-09-17 华南理工大学 Anti-eddy-current-effect transmembrane water exchange magnetic resonance imaging sequence design method
CN113406546B (en) * 2021-05-06 2022-07-26 华南理工大学 Anti-eddy-current-effect transmembrane water exchange magnetic resonance imaging sequence design method
CN114155225A (en) * 2021-12-07 2022-03-08 浙江大学 Method for quantitatively measuring exchange rate of water molecules inside and outside myelin sheaths of white matter
WO2023104000A1 (en) * 2021-12-07 2023-06-15 浙江大学 Method for quantitatively measuring exchange rate of water molecules inside and outside white matter myelin sheath

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