AN ANALYSIS METHOD OF DYNAMIC CONTRAST-ENHANCED MRI
20220018924 · 2022-01-20
Inventors
- RUILIANG BAI (HANGZHOU, ZHEJIANG PROVINCE, CN)
- ZEJUN WANG (HANGZHOU, ZHEJIANG PROVINCE, CN)
- GUANGXU HAN (HANGZHOU, ZHEJIANG PROVINCE, CN)
Cpc classification
A61B5/055
HUMAN NECESSITIES
A61B2576/00
HUMAN NECESSITIES
G06T2207/10096
PHYSICS
G01R33/5601
PHYSICS
International classification
Abstract
The present invention discloses an analysis method for dynamic contrast-enhanced magnetic resonance image. Firstly, the time-series signal of vascular contrast agent concentration, AIF, of biological individual is obtained from DCE-MRI time-series data. Secondly, perform the nonlinear least sum of square fitting by using the full Shutter-Speed model (SSM.sub.full) and the simplified vascular Shutter-Speed model (SSM.sub.vas) on the DCE-MRI time-series signal of each pixel, and the fitting results of DCE-MRI time-series signal are obtained. Thirdly, the corrected Akaike Information Criterion (AIC.sub.C) score is used to comparing the DCE-MRI time-series signal fitting results to select the optimal model. If the optimal model is SSM.sub.full, distribution maps of five physiological parameters. K.sup.trans, p.sub.b p.sub.o, k.sub.bo, and k.sub.io, are produced after fitting; if the optimal model is SSM.sub.vas, distribution maps of three physiological parameters, K.sup.trans, p.sub.b, and k.sub.bo, are produced after fitting. Finally, perform error analysis on the k.sub.io and k.sub.bo, resulting the final distribution maps of k.sub.io and k.sub.bo along with distribution maps of parameters K.sup.trans, p.sub.b, p.sub.o. This method can improve the estimation accuracy of K.sup.trans, p.sub.b, p.sub.o, k.sub.bo and k.sub.io.
Claims
1: An analysis method for dynamic contrast-enhanced magnetic resonance images (DCE-MRI), which is characterized by the analysis steps described below: (1) obtaining the biological individual's vascular contrast agent concentration as a function of time from the time-series DCE-MRI data; (2) according to the time-series signal of vascular contrast agent concentration in step (1), fitting the DCE-MRI time-series signal of each pixel by the nonlinear least sum of square algorithm using the Full Shutter-Speed model (SSM.sub.full) and the Simplified Shutter-Speed model (SSM.sub.vas) respectively, and obtaining the DCE-MRI signal fitting results of SSM.sub.full model and SSM.sub.vas model of each pixel; (3) using corrected Akaike information criterion (AIC.sub.c) to score and compare the DCE-MRI signal fitting results of the SSM.sub.full model and the SSM.sub.vas model in each pixel, according to the score from the corrected Akaike information criterion evaluating the SSM.sub.full model and the SSM.sub.vas model in each pixel, selecting the optimal model from the SSM.sub.full model and the SSM.sub.vas model for each pixel; (4) carrying out fitting according to the optimal model selected in step (3); if the optimal model being SSM.sub.full model, producing distribution maps of five groups of physiological parameters produced after fitting; the five groups of physiological parameters being the contrast agent (CA) volume transfer constant between blood plasma and extravascular-extracellular space (K.sup.trans), intravascular water mole fraction (p.sub.b), extravascular-extracellular water mole fraction (p.sub.o), the vascular water efflux rate constant (k.sub.bo) and the cellular water efflux rate constant (k.sub.io); if the optimal model being SSM.sub.vas model, due to p.sub.o and k.sub.io not being considered as estimated parameters, obtaining only distribution maps of three groups of physiological parameters after fitting; the three groups of physiological parameters being K.sup.trans, p.sub.b and k.sub.bo. (5) performing error analysis on the k.sub.io and k.sub.bo obtained in step (4) and only reserving the pixel results with 95% confidence interval in the range of [0 s.sup.−1 20 s.sup.−1] or the lower limit of 95% confidence interval greater than 5 s.sup.−1, resulting the final k.sub.io and k.sub.bo parametric distribution maps and the K.sup.trans, p.sub.b, p.sub.o parametric distribution map.
2: The dynamic contrast-enhanced magnetic resonance image (DCE-MRI) analysis method of claim 1, wherein the basic assumption of SSM.sub.full model in Step (2) is that water molecules are in three compartments of the vascular space, extravascular-extracellular space and intracellular space and water exchange happens between vascular and extravascular-extracellular spaces and between extravascular-extracellular and intracellular spaces and no water exchange happens between vascular and intracellular spaces.
3: The dynamic contrast-enhanced magnetic resonance images (DCE-MRI) analysis method of claim 2, wherein the SSM.sub.full model's fitting parameters are K.sup.trans, p.sub.b, p.sub.o, k.sub.bo and k.sub.io.
4: The dynamic contrast-enhanced magnetic resonance image (DCE-MRI) analysis method of claim 1, wherein the basic assumption of the SSM.sub.vas model in step (2) is that water molecules are in three compartments of vascular space, extravascular-extracellular space and intracellular space and water exchange processes happen between vascular and extravascular-extracellular spaces and there is no water exchange process between vascular and intracellular space, wherein the SSM.sub.vas model ignores the effect on the magnetic resonance signal induced by the water exchange process between extravascular-extracellular space and intracellular space and the intercellular water molar fraction.
5: The dynamic contrast-enhanced magnetic resonance image analysis method of claim 4, wherein the SSM.sub.vas model includes three fitting parameters are K.sup.trans, p.sub.b and k.sub.bo, and p.sub.o and k.sub.io are fixed at 0.2 and 1000 s.sup.−1, respectively.
6: The dynamic contrast-enhanced magnetic resonance image analysis method of claim 1, wherein in step (3), if the difference between the corrected Akaike information criterion scores of the SSM.sub.full model and the corrected Akaike information criterion (AIC.sub.c) score of the SSM.sub.vas model of a pixel is no more than −10, the optimal model is the SSM.sub.full model for this pixel; if the difference between the corrected Akaike information criterion score of the SSM.sub.full model and the corrected Akaike information criterion (AIC.sub.c) score of the SSM.sub.vas model of a pixel is more than −10, then the optimal model is the SSM.sub.vas model for this pixel.
7: The analysis method of dynamic contrast-enhanced magnetic resonance image of claim 6, wherein the corrected Akaike information criterion (AIC.sub.c) score is calculated as follows:
8: The analysis method of dynamic contrast-enhanced magnetic resonance image of claim 1, wherein in step (5), the 95% confidence interval of k.sub.bo or k.sub.io in the error analysis is determined by fixing the k.sub.bo (or k.sub.io) value, and then fitting all the remaining parameters via the nonlinear least sum of square method, and then changing the k.sub.bo or k.sub.io value in the [0 s.sup.−1 20 s.sup.−1] interval in small step size and repeating the fitting until:
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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SPECIFIC DESCRIPTION OF THE EMBODIMENTS
[0039] The present invention is further described in detail below in conjunction with the accompanying figures and embodiments (e.g., head imaging).
[0040] 1. As shown in
[0041] 2. As shown in
[0042] 3. As shown in
[0043] 4. As shown in
[0044] As shown in
[0045] (4-1) As shown in
[0046] (4-1-1) in the SSM.sub.full, DCE-MRI time-series signal, T1 image and AIF (namely [CA.sub.p]) signal is imported at first.
[0047] (4-1-2) SSM.sub.full sets the initial values and ranges of the five fitting parameters, p.sub.b, p.sub.o, K.sup.trans, k.sub.io, k.sub.bo. In this embodiment, the initial values of the five parameters are 0.02, 0.2, 0.01 min.sup.−1, 3 s.sup.−1, 3 s.sup.−1, and the fitting ranges are 0.001˜0.3, 0.01˜0.65, 10.sup.−5˜1 min.sup.−1, 0˜20 s.sup.−1, 0˜20 s.sup.−1, respectively.
[0048] (4-1-3) Substitute the five parameters p.sub.b, p.sub.o, K.sup.trans, k.sub.io, k.sub.bo.
[0049] (4-1-4) Calculate the contrast agent concentration in interstitial space according to the following formula,
[CA.sub.o](T)=K.sup.transv.sub.o.sup.−1∫.sub.0.sup.T[CA.sub.p](t)exp(−K.sup.transv.sub.o.sup.−1(T−t))dt
[0050] where v.sub.o is the volume fraction of interstitial space and is linearly proportional to p.sub.o (v.sub.o=p.sub.of.sub.w), [CA.sub.p] is the concentration of CA in plasma, T is the measurement time, t is the time to proceed.
[0051] (4-1-5) R.sub.1b and R.sub.1o are obtained from the contrast agent concentration [CA], assuming that they were linearly related to the contrast agent concentration, that is, R.sub.1=R.sub.1,0+r.sub.1[CA], R.sub.1 is R.sub.1b or R.sub.1o, and r.sub.1 is the relaxation rate of contrast agent.
[0052] (4-1-6) k.sub.oi and k.sub.ob are obtained by proportional relation, because in equilibrium or steady state (homeostasis), the two water exchange processes satisfy the principle of microscopic reversibility, that is, k.sub.io/k.sub.oi=p.sub.o/p.sub.i, k.sub.bo/k.sub.ob=p.sub.o/p.sub.b, where p.sub.i=1−p.sub.b−p.sub.o.
[0053] (4-1-7) it can be obtained that the exchange matrix is X, and X is shown in the following formula,
[0054] (4-1-8) The Bloch equation considering the longitudinal .sup.1H2O relaxation and water molecule exchange can be expressed as dM/dt=XM+C, where the longitudinal magnetization vector and relaxation rate vector are M=(M.sub.b, M.sub.o, M.sub.i) and C=(M.sub.b0R.sub.1b, M.sub.o0R.sub.1o, M.sub.i0R.sub.1i, respectively. The subscript “0” represents the equilibrium state.
[0055] (4-1-9) For DCE-MRI based on Gradient Recalled Echo (GRE) type, the time-series signal strength S can be obtained by substituting parameters, and the formula is as follows:
S=1.sub.1×3M=1.sub.1×3[I−e.sup.TR.Math.X cos(α)].sup.−1(I−e.sup.TR.Math.X)M.sub.0 sin(α)
[0056] TR and α are the reputation time and flip angle of GRE sequence, respectively
[0057] (4-1-10) Compare the fitted time-series signal strength S obtained by substituting the parameters with the scanned DCE-MRI time-series signal.
[0058] (4-1-11) Judge whether the fitting results meet the fitting error requirements of nonlinear least square sum algorithm.
[0059] (4-1-12) If step (4-1-11) does not meet the requirements, adjust the substitution values of five parameters p.sub.b, p.sub.o, K.sup.trans, k.sub.io, k.sub.bo according to the parameter fitting range and nonlinear least square algorithm iteration, and start from step (4-1-3) again until the requirements of step (4-1-11) are met.
[0060] (4-1-13) If step (4-1-11) is satisfied, the p.sub.b, p.sub.o, K.sup.trans, k.sub.io, k.sub.bo of SSM.sub.full fitting can be obtained, and then p.sub.b, p.sub.o, K.sup.trans, k.sub.io, k.sub.bo parameter distributions, signal fitting results and fitting error of all pixels fitted by SSM.sub.full can be obtained.
[0061] (4-2) As shown in
[0062] (4-2-1) Firstly, DCE-MRI time-series signal, T1 signal and AIF (i.e. [CA.sub.p]) signal were imported into SSM.sub.vas.
[0063] (4-2-2) Fix p.sub.o=0.2 and k.sub.io=1000 s.sup.−1 in SSM.sub.vas, and set the initial values and fitting ranges of three parameters p.sub.b, K.sup.trans and k.sub.bo. In this embodiment, the initial values of the three parameters and the fitting range and steps (4-1-2) are the same.
[0064] (4-2-3) Substitute the five parameters p.sub.b, p.sub.o, K.sup.trans, k.sub.io, k.sub.bo.
[0065] (4-2-4) repeat steps (4-1-3) to (4-1-9)
[0066] (4-2-5) The parameters are substituted into the fitted signal strength S and compare S with the scanned DCE-MRI time-series signal.
[0067] (4-2-6) Judge whether the fitting results meet the fitting error requirements of nonlinear least square sum algorithm.
[0068] (4-2-7) if step (4-2-6) is not satisfied, adjust the substitution values of p.sub.b, K.sup.trans and k.sub.bo according to the parameters fitting range and nonlinear least squares sum algorithm iteration, and start from step (4-2-3) again until the requirements of step (4-2-6) are met. If step (4-2-6) is satisfied, the p.sub.b, K.sup.trans and k.sub.bo of SSM.sub.vas fitting can be obtained, and then the p.sub.b, K.sup.trans and k.sub.bo parameter distributions of all pixels fitted by SSM.sub.vas, as well as signal fitting results and fitting errors, can be obtained.
[0069] 5. As shown in
[0070] 6. As shown in
[0071] (6-1) In the error analysis after fitting, the fitting results of SSM.sub.full and SSM.sub.vas are imported firstly.
[0072] (6-2) The corrected Akaike Information Criterion scores of SSM.sub.full and SSM.sub.vas are calculated respectively. Among them, the calculation formula of corrected Akaike Information Criterion score is as follows:
[0073] where K is the number of independent parameters of the fitting model and equal to 4 and 6 for SSM.sub.vas and SSM.sub.full, respectively, N is the number of measurement points in DCE-MRI data, and log L is the maximum logarithmic likelihood probability.
[0074] (6-3) Calculate the corrected Akaike Information Criterion score difference between the two models, ΔAIC.sub.c=AIC.sub.c(SSM.sub.full)−AIC.sub.c (SSM.sub.vas).
[0075] (6-4) Judge whether AAIC.sub.c is no more than −10.
[0076] (6-5) when the conditions in step (6-4) are satisfied, it means that the pixel is more suitable for SSM.sub.full. The fitting parameter results p.sub.b, p.sub.o, K.sup.trans, k.sub.io, k.sub.bo obtained by SSM.sub.full are assigned to the final p.sub.b, p.sub.o, K.sup.trans, k.sub.io, k.sub.bo. When the conditions in step (6-4) are not met, it means that the pixel is more suitable for SSM.sub.vas. The fitting parameter results p.sub.b, K.sup.trans, k.sub.bo obtained by SSM.sub.vas are assigned to the final p.sub.b, K.sup.trans, k.sub.bo. In the process of SSM.sub.vas, p.sub.o and k.sub.io are not fitting parameters and fixed, so they have no fitting values and are set as invalid values (NaN).
[0077]
[0078]
[0079]
[0080] 7. As shown in
[0081] (7-1) When the optimal model is SSM.sub.full, the specific process of k.sub.bo (or k.sub.io) error analysis is as follows:
[0082] (7-1-1) Determine the 95% confidence interval of k.sub.bo (or k.sub.io) by fixed k.sub.bo (or k.sub.io) value, fitting all the remaining parameters of SSM.sub.full by the nonlinear least square algorithm, and then changing the value of k.sub.bo (or k.sub.io) in the interval of [0 s.sup.−1 20 s.sup.−1] in small steps, and repeat the fitting processes until:
[0083] Among them, χ.sup.2 is the reduced chi-squared value from the fitting with the k.sub.bo or k.sub.io fixed at a certain value, χ.sub.0.sup.2 is the reduced chi-squared value with all parameters optimized, F is the F distribution function, K is the number of independent parameters in the fitting model, and N is the number of measurement points in the DCE-MRI data.
[0084] (7-1-2) If the 95% confidence interval of k.sub.bo or k.sub.io is in the interval of [0 s.sup.−1 20 s.sup.−1] or the lower limit of 95% confidence interval is bigger than 5 s.sup.−1, the fitted k.sub.bo or k.sub.io are retained. When this requirement cannot be met, k.sub.bo or k.sub.io=NaN.
[0085] The (A) in
[0086] (7-2) When the optimal model is SSM.sub.vas, the specific process of k.sub.bo error analysis is as follows:
[0087] (7-2-1) Determine the 95% confidence interval of k.sub.bo by fixed k.sub.bo value, fitting all the remaining parameters of SSM.sub.vas by the nonlinear least square algorithm, and then changing the value of k.sub.bo in the interval of [0 s.sup.−1 20 s.sup.−1] in small steps, and repeat the fitting processes until:
[0088] Among them, χ.sup.2 is the reduced chi-squared value from the fitting with the k.sub.bo fixed at a certain value, χ.sub.0.sup.2 is the reduced chi-squared value with all parameters optimized, F is the F distribution function, K is the number of independent parameters in the fitting model, and N is the number of measurement points in the DCE-MRI data.
[0089] (7-2-2) If the 95% confidence interval of k.sub.bo is in the interval of [0 s.sup.−1 20 s.sup.−1] or the lower limit of 95% confidence interval is bigger than 5 s.sup.−1, the fitted k.sub.bo are retained. When this requirement cannot be met, k.sub.bo=NaN.
[0090] The (B) in
[0091] Through the above steps 1-7, p.sub.b, p.sub.o, K.sup.trans, k.sub.io, k.sub.bo distribution maps can be generated.
[0092] In the present invention, the analysis results of this method are shown in
[0093] Tumor tissues show obvious enhancement of X.sup.trans, p.sub.b and k.sub.pe*, which was in line with expectations. A large number of references show that there are vascular hyperplasia and enhanced vascular permeability in tumors. However, there is an obvious heterogeneity of k.sub.io distribution in tumors, which may represent the distribution of tumor subcells with different metabolic levels and pathology. The tumor shows a rapid decrease of k.sub.bo, which may indicate that the active transmembrane water molecule exchange of vascular is stopped in the tumor.