CN113040744B - Quantitative method for chemical exchange saturation transfer effect of living body - Google Patents

Quantitative method for chemical exchange saturation transfer effect of living body Download PDF

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CN113040744B
CN113040744B CN202110245740.1A CN202110245740A CN113040744B CN 113040744 B CN113040744 B CN 113040744B CN 202110245740 A CN202110245740 A CN 202110245740A CN 113040744 B CN113040744 B CN 113040744B
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周欣
袁亚平
娄昕
郭茜旎
孙献平
叶朝辉
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Institute of Precision Measurement Science and Technology Innovation of CAS
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Abstract

The invention discloses a quantitative method for chemical exchange saturation transfer effect of a living body, which comprises the steps of sampling to obtain a main magnetic field B0 distribution diagram; selectively saturating chemical exchange sites of exchangeable protons by a saturation pulse without applying a gradient, and sampling to obtain a first signal intensity; applying a gradient, selectively saturating the chemical exchange sites of the exchangeable protons by a saturation pulse, and sampling to obtain a second signal intensity; under the condition of not applying a gradient and not applying a saturation pulse, sampling to obtain initial signal intensity; the normalized chemical exchange saturation transfer effect was calculated. The method of the invention has important practical value, can be applied to animals and human bodies, and the quantitative result is not influenced by the magnetization transfer effect and the nuclear Euclidean effect in vivo.

Description

Quantitative method for chemical exchange saturation transfer effect of living body
Technical Field
The invention belongs to the field of magnetic resonance imaging methods, and particularly relates to a quantitative method for chemical exchange saturation transfer effect of a living body. The invention is suitable for quantifying the endogenous or exogenous chemical exchange saturation transfer effect in the in vivo magnetic resonance imaging, and the quantification result is not influenced by the magnetization transfer effect and the nuclear Euclidean effect in the living body.
Background
Magnetic Resonance Imaging (MRI) is a common clinical medical Imaging method at present, has the advantages of no invasion, no ionizing radiation, no tissue penetration depth limitation and the like, and can provide rich contrast information. However, the development of magnetic resonance molecular imaging techniques is limited by the sensitivity of detection and spatial resolution.
Chemical Exchange Saturation Transfer (CEST) is an emerging magnetic resonance molecular imaging technique. When exchangeable protons that are in chemical exchange with water protons are present, the exchangeable protons may be selectively saturated by radio frequency pulses, thereby transferring the saturation effect to the water protons. The chemical exchange saturation transfer method indirectly detects exchangeable protons through the change of water proton signals, improves the detection sensitivity by more than three orders of magnitude, and realizes millimole order magnetic resonance molecular images. When living body imaging is carried out, endogenous amide protons, creatine, mucopolysaccharide, glucose and the like can generate chemical exchange saturation transfer effect.
In vivo, other polarization transfer effects can also cause water proton signal changes, thereby affecting the quantification of the chemical exchange saturation transfer effect. Mainly includes Magnetization Transfer (MT) effect and Nuclear Ohm (NOE) effect. The endogenous chemical exchange saturation transfer effect is mainly distributed in the range of 1-4 ppm, the nuclear Euclidean effect is mainly distributed in the range of-2-5 ppm, the spectrum width of the magnetization transfer effect is wide, and the chemical exchange saturation transfer effect and the chemical shift range of the nuclear Euclidean effect are covered. The quantification of the chemical exchange saturation transfer effect in vivo is to minimize the interference of magnetization transfer and nuclear Euclidean effect.
The existing quantitative method of chemical exchange saturation Transfer is mainly based on asymmetric Magnetization Transfer Rate (MTR)asym) And (4) calculating. V.Guival-Scharen et al [ Detection of proton chemical exchange between metals and water in biological tissues.J.Magn.Reson.1998.133: p.36-45]The magnetization transfer effect and the direct saturation effect of water are assumed to be symmetric along the center of the resonance frequency of the water protons, while the chemical exchange saturation transfer effect is asymmetric. Passing water protonThe side signals are subtracted to quantify the effect of the chemical exchange saturation transfer. However, the magnetization transfer effect is not completely symmetrical along the water proton frequency in practice, and is also interfered by the nuclear euclidean effect when the two sides are subtracted, so that the chemical exchange saturation transfer effect is inaccurate in quantification.
M.Zaiss et al [ Quantitative separation of CEST effects from a magnetic transfer and spinover effects by Lorentzian-line-fit analysis of z-spectra. J.Magn.Reson.2011.211: p.149-155 ] proposed the use of a Lorentz line to fit the chemical exchange saturation transfer effect. The chemical exchange saturation transfer effect and the direct saturation effect of water are assumed to exhibit a lorentzian linear distribution. The method needs to collect more data for linear fitting, and simultaneously needs to determine the number of exchange pools and information of approximate sites for setting initial fitting values.
J.Tao et al [ MR imaging of the amide-proton transfer effect and the pH-sensitive nuclear over user effect at 9.4T.Magn.Reson.Med.2013.69: p.760-770 ] propose a three-point method for evaluating the effect of chemical exchange saturation transfer and the nuclear Euclidean effect, collect signals and signals of frequency points on both sides of the signals, respectively, and separate the effect of chemical exchange saturation transfer or the nuclear Euclidean effect by subtracting the average value on both sides of the signals from the signal value. The method needs certain prior knowledge for point selection, and simultaneously, the quantitative result is low.
In addition, other quantitative methods include the frequency-label-exchange-transfer method proposed by J.I.Friedman et al [ index detection of label solution proton spectrum via the water signal using frequency-labeled exchange (FLEX) transfer.J.Am.chem.Soc.2010.132: p.1813-1815 ]. The method needs to collect data of a plurality of exchange times for Fourier transform.
The invention provides a quantitative method for chemical exchange saturation transfer effect of a living body, which is insensitive to magnetization transfer effect and is not interfered by nuclear Euclidean effect. The method designs a new magnetic resonance imaging pulse sequence, and provides a new reference for the quantification of the chemical exchange saturation transfer effect of the living body.
Disclosure of Invention
In order to solve the above problems of the existing quantitative methods, the present invention provides a quantitative method for chemical exchange saturation transfer effect of living body, based on the following ideas:
in vivo, the chemical exchange saturation transfer effect is mainly distributed in the low-field region on the chemical shift spectrum, taking amide protons as an example, and the chemical exchange sites are located at 3.5 ppm. The nuclear Euclidean effect is distributed in a high-field area, the magnetization transfer effect covers the high-field area and a low-field area, the spectrum width reaches thousands of Hz magnitude, and the nuclear Euclidean effect is far wider than the common chemical exchange saturation transfer effect and the nuclear Euclidean effect.
The magnetic field gradients may broaden the magnetic resonance signal. Because the spectral widths of different signals are different, the effect of the gradient broadening on the signal is different. The spectral width of the chemical exchange saturation transfer effect is usually in the order of hundreds of Hz, and a broadening of 100Hz allows the chemical exchange saturation transfer effect to be significantly reduced. Whereas a broadening of 100Hz has a negligible effect on the magnetization transfer effect.
According to the above principle, exchangeable protons are selectively saturated when no gradient is applied, and sampling obtains a first signal strength SoffFirst signal strength SoffThe method simultaneously comprises a chemical exchange saturation transfer effect and a magnetization transfer effect. Then selectively saturating the exchangeable protons while applying the layer selection direction gradient, and sampling to obtain a second signal intensity SonSecond signal strength SonThe medium magnetization transfer effect is hardly affected by the gradient, and the chemical exchange saturation transfer effect is greatly reduced. By subtracting the two, the magnetization transfer effect can be eliminated, and the chemical exchange saturation transfer effect is obtained. Finally, sampling to obtain the initial signal strength S without applying a gradient and without applying saturation0The signal is normalized. The quantitative parameter S of the normalized chemical exchange saturation transfer effectCESTExpressed as:
Figure BDA0002964036710000031
in formula 1, Son-SoffCan eliminate magnetization transfer effect to obtain chemical exchange saturation conversionThe magnitude of the shift effect, by dividing by S0The signals are normalized. The positions of the nuclear Euclidean effect and the chemical exchange saturation transfer effect on a chemical shift spectrum are different, so the calculation method is naturally not influenced by the nuclear Euclidean effect.
A method for quantifying the effect of chemical exchange saturation transfer in a living body, comprising the steps of:
step 1, sampling to obtain a main magnetic field B0 distribution diagram;
step 2, without applying gradient, selectively saturating chemical exchange sites of exchangeable protons through saturation pulse, and sampling to obtain first signal intensity Soff；
Step 3, applying a gradient, selectively saturating chemical exchange sites of exchangeable protons through saturation pulses, and sampling to obtain a second signal intensity Son；
Step 4, under the condition of not applying gradient and not applying saturation pulse, sampling to obtain initial signal intensity S0；
Step 5, using the main magnetic field B0 distribution diagram, for a first signal strength SoffAnd a second signal strength SonB0 field offset correction;
step 6, calculating normalized chemical exchange saturation transfer effect SCEST：
Figure BDA0002964036710000032
The sampling in step 1, step 2, step 3 and step 4 is all fast spin echo sampling or gradient echo sampling with the same sampling parameters.
The saturation pulse in step 2 as described above has an intensity of 1 μ T and a duration of 2 s.
In step 3, the saturation pulse has an intensity of 1 μ T, a duration of 2s, and a gradient with an intensity of 11.7mT/m in the slice selection direction.
Compared with the prior art, the method has the following beneficial effects:
1. the invention provides a new magnetic resonance imaging pulse sequence and a new calculation method, and the signal is regulated and controlled by a gradient switch, so that the chemical exchange saturation transfer effect in vivo can be separated.
2. The invention only needs to collect the signals near the chemical exchange point, the sampling data is less, and the sampling time is greatly shortened.
3. The method is naturally not influenced by the Euclidean effect of the inner core of the living body.
Drawings
FIG. 1 is a flow chart of the method of the present invention;
FIG. 2 is a schematic diagram of a pulse sequence for a quantitative method of chemical exchange saturation transfer effect of a living body;
FIG. 3 is a graph showing the effect of gradient on chemical exchange saturation transfer effect and magnetization transfer effect;
FIG. 4 shows the first signal intensity S of rat brainoffAnd a second signal strength SonDistribution on chemical displacement axis;
FIG. 5 is a graph showing the effect of chemical exchange saturation transfer in rat brain calculated by the method of the present invention.
Detailed Description
The present invention will be described in further detail with reference to examples for the purpose of facilitating understanding and practicing the invention by those of ordinary skill in the art, and it is to be understood that the examples described herein are for the purpose of illustration and explanation only and are not intended to limit the invention.
Example (b):
this example was carried out on a Bruker 7T magnetic resonance imager (BioSpec 70/20). The subjects were healthy SD (Sprague-Dawley) rats weighing 309g and were imaged for the brain. The method comprises the steps of inducing and anesthetizing a rat by using mixed gas of about 4% isoflurane, maintaining the anesthesia state of the rat by using 1-2% isoflurane mixed gas, maintaining the body temperature of the rat to be stable by using a circulating water bath device, and monitoring respiration to keep the respiration of the rat to be about 50 times/min. A birdcage coil excitation and 4-channel array coil receive mode is used.
In this example, the effect of saturation transfer of amide protons by chemical exchange in rat brain is illustrated, with a signal site of 3.5 ppm. The invention can be used not only for animals but also for human bodies.
A method for quantifying the effect of chemical exchange saturation transfer in a living body, comprising the steps of:
step 1, as shown in the flow chart of fig. 1, a main magnetic field B0 distribution map is obtained by first sampling. The method for measuring the distribution diagram of the main magnetic field B0 used in this embodiment is a Water saturation displacement reference method [ Kim M et al, Water transportation shift transfer (WASSR) for chemical exchange transfer (CEST) experiments.magn resonance med.2009.61: p.1441-1450], and B0 field distribution is obtained by fast spin echo sampling in a saturation pulse frequency sweep manner. Sampling parameters: matrix 96 x 72, layer thickness 0.8mm, TR time 5s, TE time 4.7ms, echo number 12 in the echo train. Other B0 field measurement methods, such as gradient echo sampling, are equally suitable for use with the present invention.
Step 2, without applying gradient, selectively saturating chemical exchange sites of exchangeable protons through saturation pulse, and sampling to obtain first signal intensity SoffThe pulse sequence is shown in fig. 2. In the pulse sequence, a saturation pulse is applied for several seconds while the gradient switch is off, and fast spin echo sampling is started. This example uses a 1 μ T intensity, 2S duration saturation pulse to selectively saturate the chemical exchange sites of amide protons, corresponding to a signal near 3.5ppm, to obtain a first signal intensity S as a function of chemical shiftoff. Using fast spin echo sampling, the sampling parameters are kept consistent with step 1.
Step 3, applying a gradient, selectively saturating chemical exchange sites of exchangeable protons through saturation pulses, and sampling to obtain a second signal intensity SonThe pulse sequence diagram is shown in fig. 2. In the pulse sequence, a saturation pulse is continuously applied for several seconds, and simultaneously, a gradient switch is turned on, and the fast spin echo sampling is started. In this example, a signal of about 3.5ppm was selectively saturated by applying a gradient of 11.7mT/m intensity (corresponding to 500Hz/mm) in the direction of the selected layer using a saturation pulse of 1 μ T intensity and 2S duration, and a second signal intensity S was obtained as a function of chemical shifton. Using fast spin echo sampling, the sampling parameters are kept consistent with step 1. The effect of the gradient on the signal is shown in fig. 3, and the opening of the gradient can broaden the chemical exchange saturation transfer effect, so that the intensity of the chemical exchange saturation transfer effect is greatly reduced; while the effect on the transfer of magnetization over a wide spectral width is small.
Step 4, under the condition of not applying gradient and not applying saturation pulse, sampling to obtain initial signal intensity S0. Using fast spin echo sampling, the sampling parameters are kept consistent with step 1.
Step 5, using the main magnetic field B0 distribution diagram, for a first signal strength SoffAnd a second signal strength SonB0 field offset correction was performed. The present embodiment uses a smooth spline interpolation method to interpolate the first signal strength SoffAnd a second signal strength SonThe interpolation is followed by B0 field offset correction. Corrected first signal strength SoffAnd a second signal strength SonAs shown in fig. 4.
Step 6, calculating quantitative parameter S of normalized chemical exchange saturation transfer effect by using formula (1)CEST。
Figure BDA0002964036710000051
In this example, the corrected second signal strength S at the direct point-to-point position of 3.5ppmonSubtracting the corrected first signal strength SoffIs divided by the initial signal strength S0Normalized chemical exchange saturation transfer effect S can be obtainedCESTThe distribution in rat brain is shown in figure 5.
It should be noted that the described embodiments are only illustrative of the present disclosure. Numerous additions, modifications and substitutions to the details of the described embodiments may be made by those skilled in the art without departing from the spirit of the invention or exceeding the scope of the invention as defined in the appended claims.

Claims (4)

1. A method for quantifying the effect of chemical exchange saturation transfer in a living body, comprising the steps of:
step 1, sampling to obtain a main magnetic field B0 distribution diagram;
step 2, without applying gradient, selectively saturating chemical exchange sites of exchangeable protons through saturation pulse, and sampling to obtain first signal intensity Soff；
Step 3, applying a gradient, selectively saturating chemical exchange sites of exchangeable protons through saturation pulses, and sampling to obtain a second signal intensity Son；
Step 4, under the condition of not applying gradient and not applying saturation pulse, sampling to obtain initial signal intensity S0；
Step 5, using the main magnetic field B0 distribution diagram, for a first signal strength SoffAnd a second signal strength SonB0 field offset correction;
step 6, calculating normalized chemical exchange saturation transfer effect SCEST：
Figure FDA0002964036700000011
2. The method of claim 1, wherein the sampling in step 1, step 2, step 3 and step 4 is fast spin echo sampling or gradient echo sampling with the same sampling parameters.
3. The method as claimed in claim 1, wherein the saturation pulse in step 2 has an intensity of 1 μ T and a duration of 2 s.
4. The method as claimed in claim 1, wherein the saturation pulse in step 3 has an intensity of 1 μ T and a duration of 2s, and the gradient has an intensity of 11.7mT/m in the slice selection direction.
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