WO2021184471A1

WO2021184471A1 - Non-uniform field magnetic resonance system-based apparent diffusion coefficient measurment method

Info

Publication number: WO2021184471A1
Application number: PCT/CN2020/084743
Authority: WO
Inventors: 吴子岳; 罗海; 陈潇
Original assignee: 无锡鸣石峻致医疗科技有限公司
Priority date: 2020-03-17
Filing date: 2020-04-14
Publication date: 2021-09-23
Also published as: CN111351813A; CN111351813B

Abstract

A non-uniform field magnetic resonance system-based apparent diffusion coefficient measurement method, which is based on a non-uniform field nuclear magnetic resonance system, comprising a non-uniform field magnet, a nuclear magnetic resonance spectrometer, a radio frequency power amplifier, a radio frequency coil and so on. Signals are collected by means of a plurality of CPMG sequences provided with different echo intervals, and an ADC coefficient is fitted from multiple sets of signals. The method does not require a complex diffusion enhancement sequence, and the algorithm is simple. Moreover, system requirements are low, and system costs may be reduced. At the same time, the algorithm of the method is stable and not easily affected by flowing liquid, and is also suitable for substances that have small T1/T2.

Description

A method for measuring apparent diffusion coefficient based on non-uniform field magnetic resonance system

Technical field

The invention relates to the technical field of nuclear magnetic resonance, and in particular to a method for measuring the apparent diffusion coefficient based on a non-uniform field magnetic resonance system.

Background technique

Nuclear magnetic resonance technology is a technology that uses the nuclear magnetic resonance phenomenon of hydrogen protons to image or detect the composition and structure of substances. A nucleus containing a single number of protons in the human body, such as a hydrogen nucleus, has a spin motion of the protons. The spin motion of charged atomic nuclei is physically similar to a single small magnet, and the directional distribution of these small magnets is random without the influence of external conditions. When the human body is placed in an external magnetic field, these small magnets will be rearranged according to the magnetic field lines of the external magnetic field. At this time, a radio frequency pulse of a specific frequency is used to excite the atomic nuclei, and the spins (small magnets) of these atomic nuclei are deflected and resonance occurs. This is the phenomenon of nuclear magnetic resonance. After the radio frequency pulse is stopped, the excited atomic nucleus (resonant small magnet) will gradually return to the state before the excitation. During the recovery process, the electromagnetic wave signal will be released, and the magnetic resonance pattern will be obtained after receiving and processing the nuclear magnetic resonance signal through special equipment. Or the composition and structure information of the substance.

Molecules in matter have a certain degree of diffusion motion, and the direction is random, which is called thermal motion of molecules or Brownian motion. If the diffusion motion of water molecules is not restricted in any way, we call it free diffusion. In the human body, the diffusion and movement of water molecules such as cerebrospinal fluid and urine are relatively small and are regarded as free diffusion. In fact, due to the restriction of the surrounding medium, the diffusion of water molecules in biological tissues will be restricted to varying degrees, which is called restricted diffusion. The diffusion of water molecules in general tissues belongs to restricted diffusion. The apparent diffusion coefficient is a physical quantity that describes the ability of water molecules to diffuse in tissues. After the magnetic resonance signal is excited, the diffusion movement of water molecules in the direction of the gradient magnetic field will cause the attenuation of the magnetic resonance signal. If the water molecules diffuse freely in the direction of the gradient magnetic field, the greater the diffusion distance during the application of the gradient magnetic field, the more experienced The greater the magnetic field changes, the more obvious the tissue signal attenuation. Therefore, the apparent diffusion coefficient of an object can be measured by nuclear magnetic resonance technology, thereby indirectly reflecting the characteristics of the object's microstructure and its changes.

In magnetic resonance imaging technology, the apparent diffusion coefficient is widely used as an important clinical diagnostic index. Generally, measurement is performed by diffusion-weighted imaging technology (DWI), such as SE-EPI sequence, that is, spin echo sequence (SE) for diffusion gradient encoding, and plane echo sequence (EPI) for signal readout. In a non-uniform magnetic field magnetic resonance system, a similar diffusion-weighted imaging technique is introduced to measure the apparent diffusion coefficient of a substance. Several typical pulse sequences for measuring apparent diffusion coefficient are shown in Figure 1.

Figure 1a) shows the SE-CPMG sequence, which is based on the spin echo for diffusion gradient encoding, and then uses the ultra-fast CPMG sequence for signal readout.

Figure 1b) shows the DSE-CPMG sequence, which is based on the double-echo sequence for diffusion gradient encoding, and also uses the ultra-fast CPMG sequence for signal readout. This method can reduce the impact of low-speed liquid flow.

Figure 1c) is the STE-CPMG sequence, which is based on the stimulated echo sequence for diffusion gradient coding. This method can reduce the impact of T1 recovery. When the T1/T2 of the detected object is relatively small, the ADC can be used to measure the ADC to improve the accuracy of the measurement. Spend.

In the prior art, the ADC measurement pulse sequence is composed of a diffusion gradient encoding module and a signal readout module. Because in the non-uniform field MRI system, the gradient magnetic field is very large, usually 2 to 3 orders of magnitude higher than the gradient field of the conventional MRI system, and it is impossible to control the gradient magnetic field to change during the signal readout stage (DWI technology in the MRI system, In the signal readout stage, the gradient field can be controlled to decrease). Therefore, it is necessary to adopt an ultra-fast signal readout module to reduce the influence of the diffusion effect in the process of reading the signal. For example, reference documents (Rata, DG, et al. (2006). "Self-diffusion measurements by a mobile single-sided NMR sensor with improved magnetic field gradient. "J Magn Reson 180(2): 229-235.) used in The echo interval is 40us. This places very high requirements on the spectrometer equipment, radio frequency power amplifier and radio frequency coil of the nuclear magnetic resonance system.

In non-uniform field NMR systems, CPMG sequences are usually used to acquire signals. The strong gradient field existing in the non-uniform field can not only play the role of frequency encoding in the CPMG sequence, but also always have the role of diffusion encoding. That is to say, if the echo interval of the CPMG sequence is larger, the signal is lower. In the reference [M.D. Hurlimann. Diffusion and Relaxation Effects in General Stray Field NMR Experiments. J. Magn. Reson 148, 367-378 (2001)], the influence of the diffusion effect on the CPMG signal is analyzed, which can be described by the following formula:

Among them, γ is the magnetic rotation ratio, D is the ADC coefficient of the substance, G is the size of the gradient magnetic field, and τ is the echo interval of the CPMG sequence. It can be seen from this formula that the CPMG signal is related to the ADC coefficient, gradient field and echo interval of the substance. Therefore, ADC coefficients can be estimated by collecting CPMG signals with different echo times.

Summary of the invention

The invention aims to provide a method for measuring the apparent diffusion coefficient based on a non-uniform field magnetic resonance system, which has a stable algorithm and is not easily affected by flowing liquids, and is also suitable for substances with small T1/T2.

In order to achieve the above objectives, the present invention is achieved by adopting the following technical solutions:

The invention discloses a method for measuring the apparent diffusion coefficient based on a non-uniform field magnetic resonance system, which comprises the following steps:

S100. Collect M groups of echo signals in a non-uniform field nuclear magnetic resonance system, the echo signals are a four-dimensional array S(m, n, a, p),

The first dimension is the echo interval vector τ, the length is M,

The second dimension is the length of the echo chain, the length is N,

The third dimension is the average number of times A,

The fourth dimension is the number of sampling points of a single read data, the number is P;

S200. Data preprocessing, converting the signal S(m, n, a, p) into a two-dimensional array of S′(m, n):

S210. Perform Fourier transform on the fourth dimension of the signal S to obtain frequency domain data, keep the low frequency part and average it,

S220, average the third dimension,

S230: Take a logarithm of all data;

S300, equivalent time constant T(m) estimation:

Fit S′(m,n) line by line according to the following formula

Where τ(m) is the m-th element in the echo interval vector τ, and C ₁ is an unknown constant;

S400, ADC coefficient D estimation:

Fit according to the following formula

Where γ is the magnetic rotation ratio, G is the magnitude of the gradient magnetic field, and C ₂ is an unknown constant.

Preferably, in step S100, in the non-uniform field nuclear magnetic resonance system, an excitation pulse, a refocusing pulse, and a constant gradient field are applied,

The flip angle of the excitation pulse is θ, followed by a number of convergent pulses, and the flip angle of the convergent pulse is 2θ;

The phase difference between the excitation pulse and the first refocusing pulse is 90 degrees, the time interval between the excitation pulse and the first refocusing pulse is τ/2, the first refocusing pulse to the first sampling window The time interval is τ/2; the time interval between refocusing pulses is the echo interval, and N echo signals are collected for one excitation.

Preferably, the constant gradient field is the natural gradient field of the magnet.

Preferably, the echo signals are collected multiple times and the average value is calculated.

Preferably, the echo interval is τ.

Preferably, the echo interval τ is changed, M measurements are performed, and M groups of echo signals are collected.

Preferably, the non-uniform field nuclear magnetic resonance system includes a console, a nuclear magnetic resonance spectrometer, a magnet, and a radio frequency system,

The console is connected with the nuclear magnetic resonance spectrometer, sending instructions to control the parameter selection of the measurement sequence, ROI positioning, receiving the magnetic resonance signals collected by the spectrometer, and completing real-time data processing;

The magnet is a permanent magnet design;

The radio frequency system mainly includes a radio frequency power amplifier, a preamplifier, a transceiving switch, and a radio frequency coil. The radio frequency coil can transmit excitation signals and receive magnetic resonance signals through the transceiving switch.

Preferably, the magnet is a unilateral permanent magnet.

The beneficial effects of the present invention:

1. The present invention is based on a non-uniform field nuclear magnetic resonance system, including non-uniform field magnets, nuclear magnetic resonance spectrometers, radio frequency power amplifiers and radio frequency coils, etc., through multiple CPMG sequences with different echo intervals to collect signals from multiple sets of signals Fit the ADC coefficients.

2. The present invention does not require a complicated diffusion enhancement sequence, the algorithm is simple, and the system requirements are low, and the system cost can be reduced.

3. The method of the present invention has a stable algorithm, is not easily affected by flowing liquid, and is also suitable for substances with a small T1/T2.

Description of the drawings

Figure 1 is a schematic diagram of an ADC measurement pulse sequence based on a non-uniform field nuclear magnetic resonance system in the prior art;

Figure 2 is a schematic diagram of a non-uniform field nuclear magnetic resonance system for measuring apparent diffusion coefficient;

Figure 3 is a schematic diagram of the apparent diffusion coefficient measurement sequence based on a non-uniform field nuclear magnetic resonance system;

Figure 4 shows CPMG measurement data with different echo intervals with pure water as the test substance;

Figure 5 shows the equivalent time constant measured by CPMG sequences with different echo intervals using pure water as the test substance.

Detailed ways

In order to make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described in detail below in conjunction with the accompanying drawings.

In this application:

NMR: Nuclear Magnetic Resonance, Nuclear Magnetic Resonance Technology

MRI: Magnetic Resonance Imaging, Magnetic Resonance Imaging

K-space: K-space, the frequency domain space of magnetic resonance signals

DWI: Diffusion Weighted Imaging, Diffusion Weighted Imaging or Diffusion Weighted Imaging

T1: Time constant for regrowth of longitudinal magnetization after RF-pulse, longitudinal magnetization vector recovery time constant

T2: Time constant for decay of transverse magnetization after RF-pulse, transverse magnetization vector decay time constant

TR: Repetition Time, repetition time or repetition period

ADC: Apparent diffusion coefficient, apparent diffusion coefficient

EPI: Echo planar imaging, planar echo imaging technology

CPMG: a NMR pulse sequence named by several scientists (Carr, Purcell, Meiboom, Gill), NMR sequence named by Carr, Purcell, Meiboom, Gill, etc.

SE-EPI: Spin echo-echo planar imaging, spin echo-plane echo sequence

SE-CPMG: Spin echo-CPMG sequence, spin echo-CPMG sequence

DSE-CPMG: Dual spin echo-CPMG sequence, dual spin echo-CPMG sequence

STE-CPMG: Stimulated echo-CPMG sequence, stimulated echo-CPMG sequence

As shown in Figure 2, the non-uniform field nuclear magnetic resonance system used to measure the apparent diffusion coefficient is mainly composed of four parts: the console, the nuclear magnetic resonance spectrometer, the magnet and the radio frequency system;

The console is connected with the spectrometer, sends instructions to control the parameter selection of the measurement sequence, ROI positioning, and receives the magnetic resonance signals collected by the spectrometer to complete real-time data processing.

Magnets are generally designed as permanent magnets. For example, a unilateral permanent magnet still has a highly non-uniform magnetic field in the ROI.

The radio frequency system mainly includes a radio frequency power amplifier, a preamplifier, a transceiver switch and a radio frequency coil. The radio frequency coil can transmit excitation signals and receive magnetic resonance signals through the transceiver switch.

ADC coefficient measurement sequence:

Figure 3 shows a schematic diagram of the apparent diffusion coefficient measurement sequence of a non-uniform field NMR system, that is, a typical θ-2θ-2θ-2θ...... RF pulse sequence: the first excitation pulse flip angle is θ, followed by Several refocusing pulses with a flip angle of 2θ; the phase difference between the first excitation pulse and the first refocusing pulse is 90 degrees, and the time interval between the first excitation pulse and the first refocusing pulse is τ/2, The time interval between the first refocusing pulse and the first sampling window is τ/2; the time interval between the refocusing pulses is τ, which is called the echo interval. The constant gradient field is the natural gradient field of the magnet and does not need to be controlled. Collect N echo signals in one excitation. Usually it is necessary to acquire the signal multiple times, and improve the signal-to-noise ratio by averaging the signal.

In order to estimate the ADC coefficients, it is necessary to change the echo interval τ to collect M groups of echo signals.

ADC coefficient estimation method

The collected signal is represented as a 4-dimensional array S(m, n, a, p), the first dimension corresponds to different echo intervals, that is, the corresponding echo interval vector τ, the length is M; the second dimension is the echo chain Length, the length is N; the third dimension is the average number of times A; the fourth dimension is the number of sampling points of a single read data, which is P. The ADC coefficient estimation based on the four-dimensional array mainly includes the following 3 steps,

Data preprocessing includes:

Preprocessing step 1. Perform Fourier transform on the fourth dimension of the signal S to obtain frequency domain data; only the low frequency part is retained and averaged;

Preprocessing step 2, average the third dimension;

Preprocessing step 3, take the logarithm of all data;

After data preprocessing, the signal S (m, n, a, p) is converted into a two-dimensional array of S'(m, n).

Equivalent time constant estimation:

Fit S′(m,n) line by line according to the following formula

Where τ(m) is the m-th element in the echo interval vector τ, and C ₁ is an unknown constant. Fit the equivalent time constant T(m)

Estimate the ADC coefficient D through the equivalent time constant: Fit according to the following formula

Among them, γ is the magnetic rotation ratio, G is the magnitude of the gradient magnetic field, which is a known quantity determined in advance, and C ₂ is an unknown constant.

The estimated parameter D is the ADC coefficient.

Experimental results:

The pure water is detected on the nuclear magnetic resonance system designed in the scheme of the present invention. The main parameters include the B0 field of the ROI area is 0.07T, the gradient field is 180Gauss/cm, the time interval of the CPMG sequence is 640us, 740us, 840us, 940us, 1040us and 1140us in six groups, the echo chain length of the CPMG sequence is 100, average 32 times, the number of echo sampling points is 64.

Figure 4 shows the CPMG measurement data after the preprocessing step 1 and the preprocessing step 2 of the present invention. It can be seen that the attenuation degree of the CPMG sequence acquisition signal with different echo time intervals is different. This difference is described by formula (1) The manifestation of the diffusion effect.

Fig. 5 is the result after the preprocessing step and the equivalent time constant estimation step of the present invention. It can be seen that the equivalent time constant has a good linear relationship ^{with τ 2.}

Furthermore, through linear fitting and formula (3), the ADC coefficient of pure water can be estimated to be 1.93e-3mm2/s, which is close to the theoretical value.

Of course, the present invention can also have various other embodiments. Without departing from the spirit and essence of the present invention, those skilled in the art can make various corresponding changes and modifications according to the present invention, but these corresponding changes And the deformation should belong to the protection scope of the appended claims of the present invention.

Claims

A method for measuring apparent diffusion coefficient based on a non-uniform field magnetic resonance system, which is characterized in that it comprises the following steps:

S100. Collect M groups of echo signals in a non-uniform field nuclear magnetic resonance system, the echo signals are a four-dimensional array S(m, n, a, p),

The first dimension is the echo interval vector τ, the length is M,

The second dimension is the length of the echo chain, the length is N,

The third dimension is the average number of times A,

The fourth dimension is the number of sampling points of a single read data, the number is P;

S200. Data preprocessing, converting the signal S(m, n, a, p) into a two-dimensional array of S′(m, n):

S210. Perform Fourier transform on the fourth dimension of the signal S to obtain frequency domain data, keep the low frequency part and average it,

S220, average the third dimension,

S230: Take a logarithm of all data;

S300, equivalent time constant T(m) estimation:

Fit s′(m,n) line by line according to the following formula

Where τ(m) is the m-th element in the echo interval vector τ, and C 1 is an unknown constant;

S400, ADC coefficient D estimation:

Fit according to the following formula

Where γ is the magnetic rotation ratio, G is the magnitude of the gradient magnetic field, and C 2 is an unknown constant.
The measurement method according to claim 1, characterized in that: in step S100, in the non-uniform field nuclear magnetic resonance system, an excitation pulse, a refocusing pulse, and a constant gradient field are applied,

The flip angle of the excitation pulse is θ, followed by a number of convergent pulses, and the flip angle of the convergent pulse is 2θ;

The phase difference between the excitation pulse and the first refocusing pulse is 90 degrees, the time interval between the excitation pulse and the first refocusing pulse is τ/2, the first refocusing pulse to the first sampling window The time interval is τ/2; the time interval between refocusing pulses is the echo interval, and N echo signals are collected for one excitation.
The measurement method according to claim 2, wherein the constant gradient field is the natural gradient field of the magnet.
The measurement method according to claim 2 or 3, wherein the echo signal is collected multiple times and the average value is calculated.
The measurement method according to claim 4, wherein the echo interval is τ.
The measurement method according to claim 5, wherein the echo interval τ is changed, M measurements are performed, and M groups of echo signals are collected.
The measurement method according to claim 6, wherein the non-uniform field nuclear magnetic resonance system includes a console, a nuclear magnetic resonance spectrometer, a magnet, and a radio frequency system,

The console is connected with the nuclear magnetic resonance spectrometer, sending instructions to control the parameter selection of the measurement sequence, ROI positioning, receiving the magnetic resonance signals collected by the spectrometer, and completing real-time data processing;

The magnet is a permanent magnet design;

The radio frequency system mainly includes a radio frequency power amplifier, a preamplifier, a transceiving switch, and a radio frequency coil. The radio frequency coil can transmit excitation signals and receive magnetic resonance signals through the transceiving switch.
The measurement method according to claim 7, wherein the magnet is a single-sided permanent magnet.