CN105699923A - Magnetic resonance imaging method for measuring R2, R2* and R2' parameter image of tissue in noninvasive and dynamic manner - Google Patents
Magnetic resonance imaging method for measuring R2, R2* and R2' parameter image of tissue in noninvasive and dynamic manner Download PDFInfo
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Abstract
本发明公开了一种利用组织不同脱氧血红蛋白含量具有不同程度的磁敏感特性,通过使用非对称自旋回波磁共振成像序列,采用周期移动180度回聚射频脉冲位置的策略,在每个周期内让180度回聚脉冲对称分布在TE/2时间的两侧,得到高时间分辨率的多回波图像的技术;进一步,针对采集得到的多回波信号,以相应的180度回聚脉冲移动周期长度为窗宽进行移动估计,并使用最小二乘估计根据信号衰减指数模型同时得到R2、R2*和R2’的动态参数图像。使用这种方法可以得到高时间分辨率动态R2、R2*和R2’参数图像,且能显示任意感兴趣区域的动态曲线。
The invention discloses a magnetic sensitivity characteristic of different degrees by using different deoxygenated hemoglobin contents in tissues, by using an asymmetric spin echo magnetic resonance imaging sequence, and adopting a strategy of periodically moving 180 degrees to refocus the radio frequency pulse position, in each cycle Let the 180-degree refocusing pulses be symmetrically distributed on both sides of the TE/2 time to obtain multi-echo images with high time resolution; further, for the collected multi-echo signals, move with the corresponding 180-degree refocusing pulses The period length is the window width for motion estimation, and the dynamic parameter images of R2, R2* and R2' are simultaneously obtained according to the signal attenuation exponential model by using the least square estimation. Using this method, dynamic R2, R2* and R2' parameter images with high temporal resolution can be obtained, and dynamic curves of any region of interest can be displayed.
Description
技术领域 technical field
本发明属于磁共振成像(MRI)技术领域,具体是一套基于磁共振成像技术动态无创地定量测量不同组织的本征弛豫时间R2,R2*和R2’的方法。 The invention belongs to the technical field of magnetic resonance imaging (MRI), in particular to a set of methods for dynamically and noninvasively and quantitatively measuring the intrinsic relaxation times R2, R2* and R2' of different tissues based on the magnetic resonance imaging technology.
背景技术 Background technique
磁敏感作为一种重要的对比机制,在磁共振技术中有着广泛的应用。举例来说,血氧水平依赖成像(BOLD)技术就是基于脱氧血红蛋白的顺磁特性发展起来的成像手段,目前已经广泛应用到头部、肾脏和骨骼肌在不同条件(缺氧、高碳酸和缺血)的功能评价。 Susceptibility, as an important contrast mechanism, has a wide range of applications in magnetic resonance techniques. For example, blood oxygen level-dependent imaging (BOLD) is an imaging method developed based on the paramagnetic properties of deoxygenated hemoglobin. Blood) functional evaluation.
在磁共振成像中,磁敏感效应会影响R2*参数,而R2*是组织信号的自由衰减率,通常使用单指数衰减模型来拟合。而R2*包含了两个成分:(1)一个是不可逆的成分R2,(2)另一个是可逆的R2’,反映了磁敏感引起的像素内散相程度。在单指数模型中,R2*=R2+R2’。通常而言,组织磁敏感性使用R2*而不是R2’来衡量,但其实后者不会受到由病理原因引起的R2的变化的影响。另一方面,R2*和R2成像在动态磁敏感灌注加权成像(DSC-PWI)和功能磁共振成像(fMRI)研究中被结合使用来对组织的血液动力学信息进行定量描述。例如,Prinster等人利用BOLD技术,以在低氧和高碳酸条件下弛豫时间的相对变化比(ΔR2/ΔR2*)作为一种指标用来区分含有大血管和小血管的体素。进一步,采用在注射顺磁性造影剂后的R2和R2*成像信息用来对脑部血管的平均大小提供定量信息。综上所述,一种能够同时获得R2和R2*准确定量信息的序列是十分必要的。 In magnetic resonance imaging, susceptibility effects affect the R2* parameter, and R2* is the free decay rate of the tissue signal, usually fitted using a single-exponential decay model. And R2* contains two components: (1) one is the irreversible component R2, and (2) the other is the reversible R2', which reflects the degree of phase dispersion in the pixel caused by magnetic sensitivity. In a single exponential model, R2*=R2+R2'. Typically, tissue susceptibility is measured using R2* rather than R2', although the latter is not affected by changes in R2 due to pathological causes. On the other hand, R2* and R2 imaging are combined in dynamic susceptibility perfusion-weighted imaging (DSC-PWI) and functional magnetic resonance imaging (fMRI) studies to quantitatively describe tissue hemodynamic information. For example, Prinster et al. used the BOLD technique to use the relative change ratio of relaxation time (ΔR2/ΔR2*) under hypoxic and hypercapnic conditions as an indicator to distinguish voxels containing large vessels from small vessels. Further, R2 and R2* imaging information after paramagnetic contrast agent injection was used to provide quantitative information on the mean size of cerebral vessels. To sum up, a sequence that can obtain accurate quantitative information of R2 and R2* at the same time is very necessary.
通常来说,可以分别采用多回波自旋回波序列和多回波梯度回波序列来得到R2和R2*信息。这种方法除了时间较长的缺点以外,两次扫描分别得到R2和R2*的策略可能会由于两次扫描之间的生理变化导致较大的R2和R2*之间的估计误差。最近,有人提出了一种梯度回波采样自由衰减回波(GESFIDE)序列用来同时得到R2和R2*信息。在此序列中,利用多个梯度回波来同时采集90°激发脉冲后的自由衰减磁化强度和180°重聚焦脉冲后的自旋磁化强度。R2*可以利用自由衰减过程中的磁化强度来得到,而R2则可以通过比较180°脉冲左右对称位置的回波强度来得到。一种与GESFIDE类似的称做梯度回波采样自旋回波(GESSE)序列也被提出用来同时得到R2和R2*信息,在此序列中,利用多个梯度回波来同时采集自旋回波形成和衰减过程中的磁化强度。但是,以上两种方法都采用了传统的笛卡尔K空间采集策略,导致成像速度较慢,不能满足诸如DSC-PWI或fMRI应用中高时间分辨率的要求。最近,又有人提出了一种可以动态得到R2和R2*信息的多回波自旋和梯度回波(SAGE)回波平面成像(EPI)序列。但是,在此序列中,由短射频(RF)脉冲时间导致的非理想选层轮廓会导致在180°重聚焦脉冲前后采集到的图像层面轮廓不匹配的问题,而这一问题会在后续R2和R2*的定量计算中产生较大的估计误差。 Generally speaking, R2 and R2* information can be obtained by using a multi-echo spin echo sequence and a multi-echo gradient echo sequence, respectively. In addition to the disadvantage of longer time for this method, the strategy of obtaining R2 and R2* from two scans may cause a large estimation error between R2 and R2* due to physiological changes between the two scans. Recently, a gradient echo sampled free decay echo (GESFIDE) sequence was proposed to simultaneously obtain R2 and R2* information. In this sequence, multiple gradient echoes are used to simultaneously acquire the free-decay magnetization after the 90° excitation pulse and the spin magnetization after the 180° refocusing pulse. R2* can be obtained by using the magnetization intensity during the free decay process, while R2 can be obtained by comparing the echo intensity at the left and right symmetrical positions of the 180° pulse. A sequence called gradient echo sampled spin echo (GESSE) similar to GESFIDE is also proposed to obtain R2 and R2* information simultaneously. In this sequence, multiple gradient echoes are used to simultaneously acquire spin echoes to form and magnetization during decay. However, the above two methods both adopt the traditional Cartesian K-space acquisition strategy, resulting in slow imaging speed, which cannot meet the requirements of high temporal resolution in applications such as DSC-PWI or fMRI. Recently, a multi-echo spin and gradient echo (SAGE) echo planar imaging (EPI) sequence that can dynamically obtain R2 and R2* information has been proposed. However, in this sequence, non-ideal slice-selection profiles caused by short radio frequency (RF) pulse times lead to a mismatch of image slice profiles acquired before and after the 180° refocusing pulse, which will be discussed later in R2 Large estimation error occurs in the quantitative calculation of R2* and R2*.
如上所述,已有的方法存在着时间分辨率低或者估计误差较大的缺点。所以,一种可以同时且准确得到R2,R2*和R2’信息的动态方法是急需的。 As mentioned above, existing methods have the disadvantages of low temporal resolution or large estimation errors. Therefore, a dynamic method that can simultaneously and accurately obtain R2, R2* and R2' information is urgently needed.
发明内容 Contents of the invention
在本专利中,我们提出了一种周期性移动180°脉冲位置的多回波非对称自旋回波(psMASE)序列。在此序列中,由于是在自旋回波形成和衰减过程中进行信号采集,避免了层面轮廓不匹配的问题。进一步,为了提高动态成像的时间分辨率,一种移动窗估计的策略被引入到R2,R2*和R2’的定量计算中,移动窗的长度与psMASE序列的周期长度相同。以周期为3TR举例,具体的方法流程如图1所示。 In this patent, we propose a multi-echo asymmetric spin-echo (psMASE) sequence that periodically shifts the pulse position by 180°. In this sequence, since the signal is acquired during spin echo formation and decay, the problem of slice profile mismatch is avoided. Further, in order to improve the temporal resolution of dynamic imaging, a strategy of moving window estimation is introduced into the quantitative calculation of R2, R2* and R2', and the length of the moving window is the same as the period length of the psMASE sequence. Taking the period as 3TR as an example, the specific method flow is shown in FIG. 1 .
对于传统的多回波ASE序列,180°重聚焦脉冲的位置可以灵活设定。理论上,一个确定的180°脉冲位置对于多回波(通常2-6个回波)的数据采集可以依据单指数模型得到R2,R2’和R2*信息。实际上,为了得到更为准确的R2,R2’和R2*信息,180°脉冲通常需要移动几次位置来获得更多的回波数据。本专利提出了一种周期性移动180°脉冲位置的多回波非对称自旋回波序列,以周期为3TR和四EPI回波举例,序列示意图如图2所示。在psMASE序列中,180°脉冲不是线性移动而是周期性移动的。 For traditional multi-echo ASE sequences, the position of the 180° refocusing pulse can be flexibly set. Theoretically, for a certain 180° pulse position for data acquisition of multiple echoes (usually 2-6 echoes), R2, R2’ and R2* information can be obtained according to the single exponential model. In fact, in order to obtain more accurate R2, R2' and R2* information, the 180° pulse usually needs to move several times to obtain more echo data. This patent proposes a multi-echo asymmetric spin-echo sequence that periodically shifts the pulse position by 180°. Taking the cycle of 3TR and four EPI echoes as an example, the schematic diagram of the sequence is shown in Figure 2. In the psMASE sequence, the 180° pulses do not move linearly but periodically.
对于每个确定180°脉冲位置的子序列,多个EPI回波位于自旋回波位置的两侧用来采集成像数据,回波时间(TEi)定义为90°激发脉冲中心与回波k空间中心的时间间隔。当第一个EPI回波数据采集完成后,相位编码进行反转,接下来的三个回波数据采用相同的方式进行依次采集。每相邻两个回波之间的时间间隔定义为ΔTE。不同的回波位置由于与自旋回波位置具有不同的偏离,相应的不同回波位置采集得到的信号具有不同的T2*权重。依据单指数衰减模型,在距离90°脉冲不同时间采集得到的信号强度函数如下所示: For each subsequence that determines the 180° pulse position, multiple EPI echoes are located on both sides of the spin echo position to acquire imaging data, and the echo time (TE i ) is defined as the distance between the center of the 90° excitation pulse and the echo k-space center interval. When the first EPI echo data acquisition is completed, the phase encoding is reversed, and the next three echo data are sequentially acquired in the same way. The time interval between every two adjacent echoes is defined as ΔTE. Since different echo positions have different deviations from the spin echo positions, corresponding signals acquired at different echo positions have different T2* weights. According to the single exponential decay model, the signal strength function collected at different times from the 90° pulse is as follows:
其中,S(t)表示在采集时间t得到的信号,S0是90°脉冲下激发得到的磁化强度,TESE是有效自旋回波时间间隔。公式[1]可以简化表达成如下形式: Among them, S(t) represents the signal obtained at the acquisition time t, S 0 is the magnetization obtained by excitation under the 90° pulse, and TE SE is the effective spin echo time interval. Formula [1] can be simplified into the following form:
对公式[2]两边同时取自然对数,可以进一步简化为: Taking the natural logarithm on both sides of formula [2], it can be further simplified as:
具体来说,在psMASE序列中,可以灵活设定90°和180°脉冲之间的时间间隔,180°脉冲中心与TE1/2之间的时间间隔定义为τ,通过改变τ而保持回波时间TEi不变,每个回波采集得到的信号具有相同的R2权重而R2’的权重不同,所有R2’可以被有效估计。更具体来说,以周期为3TR和四EPI回波举例,如图1的步骤1所示,τ在一个周期内采用-ΔTE/2,0和ΔTE/2三个大小用来最大程度利用自旋回波位置进行数据采集来提高信噪比(SNR)。如图1的步骤3所示,在一个周期内,每个体素的R2,R2’和R2*大小可以通过下面公式拟合得到: Specifically, in the psMASE sequence, the time interval between 90° and 180° pulses can be flexibly set, the time interval between the center of the 180° pulse and TE 1/2 is defined as τ, and the echo is maintained by changing τ The time TE i is constant, the signal obtained by each echo acquisition has the same R2 weight but the R2' has different weights, and all R2' can be effectively estimated. More specifically, taking the period of 3TR and four EPI echoes as an example, as shown in step 1 of Fig. 1, τ uses three sizes of -ΔTE/2, 0 and ΔTE/2 in one period to maximize the use of Data acquisition is performed at the position of the spin echo to improve the signal-to-noise ratio (SNR). As shown in step 3 of Figure 1, within a period, the size of R2, R2' and R2* of each voxel can be fitted by the following formula:
其中,S3n+1(TEi),S3n+2(TEi)和S3n+3(TEi)表示在不同τ情况下在不同回波时间TEi采集得到的信号强度,其中TE1可以在20-80ms之间,TESE1,TESE2和TESE3表示不同τ情况下的有效自旋回波时间。 Among them, S 3n+1 (TE i ), S 3n+2 (TE i ) and S 3n+3 (TE i ) represent the signal strength collected at different echo times TE i under different τ conditions, where TE 1 It can be between 20-80 ms, TE SE1 , TE SE2 and TE SE3 represent the effective spin echo time under different τ cases.
此外,为了进一步提高时间分辨率,一种移动窗估计的策略被引入到R2,R2’和R2*的估计当中,如图1的步骤4所示。以周期为3TR举例,移动估计策略的测量方式如图3所示,移动窗的大小设置为与psMASE序列的周期大小一致。在每个TR时间内,对于每个成像层来说,在四个回波位置采集到的四张图像得到一个图像组。每个时间点的R2,R2’和R2*大小可以由相应时间点的图像组及其左右时间点的两个相邻图像组根据最小均方差原则依据公式[4]拟合得到。如图1的步骤2所示,为了提高信噪比,所有图像都利用高斯滤波器进行前处理(内核算子大小=3×3;标准差=1.5)。 In addition, in order to further improve the time resolution, a strategy of moving window estimation is introduced into the estimation of R2, R2' and R2*, as shown in step 4 of Figure 1. Taking the period as 3TR as an example, the measurement method of the motion estimation strategy is shown in Figure 3, and the size of the moving window is set to be consistent with the period size of the psMASE sequence. In each TR time, for each imaging layer, four images collected at four echo positions form an image group. The size of R2, R2' and R2* at each time point can be obtained by fitting the image group at the corresponding time point and the two adjacent image groups at the left and right time points according to the principle of minimum mean square error and formula [4]. As shown in step 2 of Figure 1, in order to improve the signal-to-noise ratio, all images are pre-processed with a Gaussian filter (kernel operator size = 3 × 3; standard deviation = 1.5).
本方法和GESSE或者GESFIDE序列相比,在同时得到R2和R2*信息方面具有三个优点。第一,ASE序列可以调控R2’的权重而保持R2的权重不变,这样R2’可以直接拟合得到,基于多回波ASE方法,R2,R2’和R2*信息可以同时得到。第二,在ASE序列中,回波个数不再受到TE时间和读出带宽的限制,并且180°重聚焦脉冲的位置可以灵活设定。第三,EPI的采集策略可以更好的结合流速衰减梯度,用来减少血管内信号的贡献并且不会引入额外的运动伪影。 Compared with GESSE or GESFIDE sequence, this method has three advantages in simultaneously obtaining R2 and R2* information. First, the ASE sequence can adjust the weight of R2' while keeping the weight of R2 unchanged, so that R2' can be directly fitted. Based on the multi-echo ASE method, R2, R2' and R2* information can be obtained simultaneously. Second, in the ASE sequence, the number of echoes is no longer limited by the TE time and readout bandwidth, and the position of the 180° refocusing pulse can be flexibly set. Third, the acquisition strategy of EPI can better combine the flow rate attenuation gradient to reduce the contribution of intravascular signals without introducing additional motion artifacts.
本方法与SAGE序列相比,由于在自旋回波形成和衰减过程中进行磁化矢量采集,避免了在SAGE序列中180°重聚焦脉冲前后采集图像导致的层面轮廓不匹配问题。 Compared with the SAGE sequence, this method avoids the problem of layer profile mismatch caused by acquiring images before and after the 180° refocusing pulse in the SAGE sequence because the magnetization vector is acquired during the spin echo formation and decay process.
总的来说,psMASE的序列设计使得R2,R2’和R2*的动态成像成为可能,同时,移动窗估计策略的引入可以进一步提高动态成像的时间分辨率。 In general, the sequence design of psMASE makes the dynamic imaging of R2, R2' and R2* possible, and at the same time, the introduction of the moving window estimation strategy can further improve the temporal resolution of dynamic imaging.
附图说明 Description of drawings
图1是无创动态测量组织R2,R2*和R2'参数图像的方法流程图(以周期为3TR举例)。 Fig. 1 is a flowchart of a method for non-invasive dynamic measurement of tissue R2, R2* and R2' parameter images (taking the cycle as 3TR as an example).
图2是psMASE序列设计图(以周期为3TR和四EPI回波举例)。。 Figure 2 is a diagram of psMASE sequence design (take the cycle of 3TR and four EPI echoes as an example). .
图3是移动窗估计策略示意图(以周期为3TR举例)。 Fig. 3 is a schematic diagram of a moving window estimation strategy (taking the period as 3TR as an example).
图4是一名志愿者的典型下肢缺血和恢复模型下的R2,R2*和R2’动态测量结果示意图。 Figure 4 is a schematic diagram of the dynamic measurement results of R2, R2* and R2' under a typical lower limb ischemia and recovery model of a volunteer.
具体实施方式 detailed description
psMASE序列扫描应在常规定位扫描和参考像扫描完成后进行,在使用过程中,受试者平躺在MR扫描床上。以下肢小腿部肌肉成像为例,一个合适的psMASE序列参数可以设置如下:fieldofview(FOV)=150×150mm2,matrixsize=70×70,repetitiontime(TR)=2000ms,TE1/TE2/TE3/TE4=60/80/100/120ms,echospace=20ms,τ=-10/0/10ms,slicethickness=6mm,SENSEfactor=2,NSA=1,echoshiftnumber=12。以上参数可以根据不同的需求进行调整。 The psMASE sequence scan should be performed after the routine positioning scan and reference image scan. During the use, the subject lies flat on the MR scan table. Taking the imaging of lower extremity calf muscles as an example, a suitable psMASE sequence parameter can be set as follows: fieldofview(FOV)=150×150mm 2 , matrixsize=70×70, repetitiontime(TR)=2000ms,TE 1 /TE 2 /TE 3 /TE 4 =60/80/100/120ms, echospace=20ms, τ=-10/0/10ms, slicethickness=6mm, SENSEfactor=2, NSA=1, echoshiftnumber=12. The above parameters can be adjusted according to different requirements.
为体现本方法可以动态测量组织R2,R2*和R2’参数图像的特点,以一个志愿者在典型的下肢缺血和恢复实验为例,受试者仰面平躺在MR扫描床上,使用充气血压带绑在右腿大腿处,使用尼龙带固定防止血压带松弛。在扫描过程中,保持受试者的头、脚和膝盖在同一水平面。首先进行静息态90s扫描,而后我们手动将血压带充气至200mmHg压强,整个充气过程在5秒内完成。在维持充气压强8分钟之后,我们迅速松开止血带。整个过程中进行psMASE序列的扫描(采用周期为3TR和四EPI回波采集),由此方法得到的腓肠肌R2,R2*和R2’的变化曲线如图4所示。 In order to reflect the characteristics of this method that can dynamically measure tissue R2, R2* and R2' parameter images, take a volunteer in a typical lower limb ischemia and recovery experiment as an example. The belt is tied to the thigh of the right leg and fixed with a nylon strap to prevent the blood pressure belt from loosening. During the scan, keep the subject's head, feet, and knees at the same level. First, a resting state 90s scan was performed, and then we manually inflated the blood pressure belt to a pressure of 200mmHg, and the entire inflation process was completed within 5 seconds. After maintaining the inflation pressure for 8 minutes, we quickly released the tourniquet. During the whole process, the psMASE sequence was scanned (acquisition with a period of 3TR and four EPI echoes), and the change curves of gastrocnemius R2, R2* and R2' obtained by this method are shown in Figure 4.
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