| Hepatocellular carcinoma(HCC)as a major cancer all over the world ranks first among all primary malignant tumor of liver(accounting for more than 90%).It has a rapid development and an extremely high malignant degree,which brings a serious threat to human life and health.At present,the increasing incidence of HCC had urged it to become one of the most common causes of cancer-related death worldwide.The main treatment for HCC includes surgical radical resection and non-operative treatment.For unresectable HCC,radiofrequency ablation(RFA)is currently one of the main approaches of non-surgical treatment and can be used as a palliative treatment for tumor reduction.In recent years,the dynamic contrast enhanced magnetic resonance imaging(DCE-MRI)with quantitative or semi-quantitative parameters has been gradually applied to the clinic.DCE-MRI acquires series dynamic images and analyzes them with the help of pharmacokinetic model,consequently obtaining a group of semi-quantitative and quantitative functional parameters.Using these parameters,DCE-MRI simulates the metabolic process of contrast agent in the liver lesion area,quantitatively analyze the changes of blood supply and perfusion and osmotic microcirculation of tumor tissue,and successfully make up for the inability of conventional MRI sequence to complete quantitative analysis.Therefore,DCE-MRI has exhibited potential in the HCC diagnosis and RFA efficacy evaluation.Part ? Application of DCE-MRI in the evaluation of HCCThe main diagnostic indicators for the screening and detection of HCC are usually serum tumor biomarkers and the multi-phase imaging.Magnetic resonance imaging(MRI)is the best imaging method for diagnosis and preoperative evaluation of HCC.Currently,MRI primarily uses conventional sequence,changes in the involved morphology and tissue signal,and the way of lesion enhancement to diagnose HCC,which however mainly depends on doctor's experience and thus lacks objectivity.DCE-MRI is a functional imaging technique to evaluate the pathophysiological properties of the lesion according to the inside abnormal microvascular system.Compared with conventional MRI scan and contrast enhancement-MRI,DCE-MRI can obtain more semi-quantitative and quantitative functional parameters,which provide imaging biomarkers such as tissue blood supply,changes in tissue perfusion and capillary permeability,etc.,in which the change of tumor tissue permeability has attracted extensive attention.At present,the commonly used DCE-MRI models for evaluating the permeability changes in tumor tissue include single-compartment model,two-compartment model and reference model,among which the two-compartment model Extended Tofts(ET)and Exchange(EX)are simpler and more feasible.ObjectiveTo explore the value of semi-quantitative parameters,perfusion parameters and permeability parameters of DCE-MRI in the evaluation of HCC,to measure vascular functional permeability parameters by using two pharmacokinetic models(ET and EX),and to analyze and compare the value of the two models in HCC diagnosis.Materials and methodsA total of 138 patients with HCC(HCC group)and 38 healthy volunteers(control group)were included,and all of them suffered conventional MRI and DCE-MRI examination.Image post-processing software OmniKinetics(O.K.GE Healthcare,China)was used to obtain the semi-quantitative parameters,perfusion parameters and the permeability parameters of pharmacokinetic model in the area of interest(ROI)of HCC lesion,paracarcinomatous liver tissues(PCLT)normal liver tissue in the control group,respectively.The differences of parameters between HCC and control groups in different groups and the differences of permeability parameters between ET and EX were compared and analyzed.Logistic regression analysis and diagnostic tests were used to evaluate the parameters of liver tissue between the two groups.Results1 Results of the semi-quantitative parameters time to peak(TTP,min),max concentration(MC,mmol/L),initial area under the concentration time curve during the first 60 sec(IAUC,mmol*min)and maximum slope(MS)are as follows:1)HCC group:0.87±0.25,1.18±0.79,1.41±0.84 and 4.20±3.01;2)PCLT:0.99±0.22,0.67±0.24,0.90±0.32 and 2.15±0.94;3)Control group:0.92±0.23,0.65±0.22,0.84±0.25 and 2.14±0.99.4)The semi-quantitative parameters in HCC group were significantly different from those of PCLT and control group(P<0.05).2 Results of perfusion parameters blood flow(BF,ml/min/100g),blood volume(BV,ml/100g)and mean transit time(MTT,min)are as follows:1)HCC group:202.00±132.0,39.34± 19.07 and 0.2510.13;2)PCLT:163.34±88.49,32.46± 13.48 and 0.277±0.12;3)Control group:139.66±74.18,25.65±12.50 and 0.24±0.12,4)In terms of perfusion parameters,BF and BV of HCC group and PCLT were significantly different from those in control group(P<0.05),while there was no significant difference in MTT between HCC group and PCLT(P=0.3016),and between HCC group and control group(P=0.3434).3 Permeability parameters3.1 Results of parameters volume transfer constant from blood plasma to extravascular extracellular space(Ktrans,min-1),rate constant for transfer from extravascular extracellular space to blood plasma(kep,min-1),volume of extravascular-extracellular space(ve),volume of blood plasma per unit volume of tissue or the ratio of blood plasma volume to tissue volume(vp)and hepatic arterial perfusion index(HPI)of ET are as follows:1)HCC group:1.13±0.74,3.10±1.84,1.91±1.38,0.29±0.21 and 0,68±0.17;2)PCLT:0.85±0.51,2.86±1.35,1.42±1.23,0.23±0.14 and 0.30±0.15;3)Control group:0.91±0.73,3.09±1.87,1.57±1.67,0.16±0.10 and 0.29±0.12.4)Comparative analysis of the permeability parameters of ET model among groups:There were statistically significant differences in Ktrans,ve,vp and HPI between HCC group and PCLT(P<0.05),while kep between the two groups showed no significant differences(P=0.0881);there were statistically significant differences in Ktrans?ve,vp and HPI between HCC and control groups(P<0.05),and kep between the two groups showed no significant differences(P=0.9498);3.2 Results of the parameters of Ktrans(min-1),kep(min-1),ve,vp,HPI and flow rate of the blood plasma through the intravascular plasma space(Fp,ml/min/100g)of EX are as follows:1)HCC group:1.85±0.8,1.69±1.07,0.78±0.20,0.31±0.20,0.57±0.26 and 1.76±0.79;2)PCLT:2.45±0.75,2.96±1.65,0.74±0.21,0.35±0.21,0.09±0.10 and 2.31±0.76;3)Control group:2.33±0.84,3.02±1.83,0.73±0.19,0.26±0.17,0.10±0.10,2.23±0.84 and 2.23±0.84.4)Comparative analysis of the permeability parameters of EX among groups:there were statistically significant differences in all parameters between HCC group and PCLT(P<0.05).The Ktrans(min-1),kep(min-1),ve,HPI and Fp between HCC group and control group showed significant differences(P<0.05),while vp between the two groups showed no significant differences(P=0.1735).4 Comparison of the parameters between ET and EX within the HCC group,PCLT and control group,respectively:In HCC group,Ktrans,kep,ve and HPI showed significant differences between ET and EX(P<0.05),while vp showed no significant differences between two models(P=0.186);in PCLT,Ktrans,vp,ve and HPI showed significant differences between ET and EX(P<0.05),while kep showed no significant differences between two models(P=0.7762);and in control group,Ktrans,ve,vp and HPI showed significant differences between ET and EX(P<0.05),while kep showed no significant differences(P=0.8136).There was a certain correlation between the parameters of the two models:In HCC group,Ktrans,kep,vp and HPI showed weak to moderate correlation,with r ranging from 0.2532 to 0.7217,in which the r value of ve showed no significant differences(P=0.9767);in PCLT,Ktrans,kep,ve,vp and HPI showed weak correlation,with r ranging from 0.2484 to 0.4303;and in control group,Ktrans,kep and ve showed weak correlation,with r ranging from 0.3290 to 0.5253,in which the r values of vp and HPI showed no significant differences(P=0.0967 and P=0.2005,respectively);5 Logistic regression analysis and diagnostic test evaluation for distinguishing HCC(p refers to probability)5.1 Semi-quantitative logistic regression model:lnp/1-p=-1.1093+0.8603×MS(model 1);the area under the ROC curve(AUC)was 0.787,with the sensitivity of 77.5%,and the specificity of 68.4%.5.2 Logistic regression model by perfusion parameters:ln-p/1-p=-0.2627+0.0505×B(model 2);the AUC was 0.709,with a sensitivity of 52.9%,and a specificity of 78.9%.5.3 Regression analysis and diagnostic test evaluation for distinguishing HCC by permeability parameters:(1)Logistic regression model for permeability parameters of ET:lnp/1-p=-8.7445+7.9343×Vp+17.5833×HPI(model 3);the AUC was 0.975,with the sensitivity of 94.9%,and the specificity of 94.7%.(2)Logistic regression model by permeability parameters of EX:lnp/1-p=-6.2373+1.3379×Ktrans+19.6095× HPI(model 4);the AUC was 0.969,with a sensitivity of 90.6%,and a specificity of 92.1%.5.4 Logistic regression model and diagnostic test evaluation for distinguishing HCC by the two models combined with the semi-quantitative and perfusion parameters(1)Logistic regression model for the combination of the parameters and ET:ln-p/1-p=-11.7921+20.1850 x HPI+6.4564 x IAUC-1.0543 x M(model 5).The AUC was 0.978,with a sensitivity of 92.8%,and a specificity of 97.4%.(2)Logistic regression model for the combination of the parameters and EX:ln-p/1-p=-5.7357+15.9189 x HPI+0.1045 x BV(model 6).The AUC was 0.975,with a sensitivity of 97.1%,and a specificity of 89.5%.Conclusions1 DCE-MRI combined with the analysis of semi-quantitative parameters,perfusion parameters and permeability parameters acquired from the pharmacokinetic model is able to provide quantitative information of HCC microcirculation,which is a supplement to the morphology and anatomy of conventional MRI sequence and has important value in evaluating the pathophysiological characteristics of HCC.2 The two pharmacokinetic permeability models,ET and EX,all have ideal diagnostic efficacy in HCC evaluation,in which EX can provide more comprehensive information.3 The better way to quantitatively diagnose HCC with MRI is to combine the semi-quantitative parameter IAUC and MS with the parameter HPI in ET,leading to the logistic regression model with the AUC of 0.978,the sensitivity of 92.8%,and the specificity of 97.4%.Part ? Application of DCE-MRI in short-term efficacy evaluation after RFA for HCCThe incidence and fatality rates of HCC remain high.The main treatment for HCC includes surgical radical resection and non-operative treatment.For unresectable HCC,radiofrequency ablation(RFA)is currently one of the main approaches of non-surgical treatment and can be used as a palliative treatment for tumor reduction.The semi-quantitative parameters of DCE-MRI and the parameters of perfusion and permeability reflect the changes of microcirculation in the lesion area after treatment,which provides more pathophysiological information for evaluating the efficacy RFA in HCCObjectiveWe tried to analyze the role of semi-quantitative parameters,perfusion parameters and permeability parameters of DCE-MRI in the evaluation of HCC after RFA,in order to aid clinicians in achieving accurate evaluation and guidance of making further accurate treatment plans.Materials and methodsSixty-nine patients with HCC who suffered DCE-MRI after the treatment of RFA were included,among which 42 cases had complete ablation and 27 had residual near the ablation zone or relapse.The participants for HCC group and control groups were the same as Part One.The carcinoma was only treated with RFA.Professional DCE-MRI image post-processing software OmniKinetics(O.K.,GE Healthcare,China)was used to delineate the ROI of HCC region for RFA,residual region,and liver tissue near the ablation region,in order to obtain the semi-quantitative parameters and perfusion parameters of the dynamic enhancement curve of DCE-MRI,as well as the permeability parameters of the pharmacokinetic model.The differences of parameters between HCC region for RFA and residual region in different tissues and the differences of permeability parameters between ET and EX were compared and analyzed.ResultsResults in the complete ablation group1 Results of the semi-quantitative parameters TTP(min),MC(mmol/L),IAUC(mmol*min)and MS are as follows:1)HCC region for RFA:1.17±0.37,0.23±0.13,0.22±0.16 and 0.84±0.44;2)Liver tissue near the ablation region:1.01±0.21,0.66±0.23,0.91±0.32 and 2.04±0.90;3)HCC group and control group:same as the corresponding proportion in Part One.4)Comparison analysis of semi-quantitative parameters among groups showed that the TTP,MC,IAUC and MS of HCC region for RFA were significantly different from those of liver tissue near the ablation region,the control group and HCC group(P<0.05).2.Results of perfusion parameters BF(ml/min/100g),BV(ml/100g)and MTT(min)are as follows:1)HCC region for RFA:16.20±10.76,3.48±1.34,and 1.50±0.10;2)Liver tissue near the ablation region:152.34±72.96,31.69±12.32,and 0.29±0.17;3)HCC group and control group:same as the corresponding proportion in Part One.4)Comparison analysis of perfusion parameters among groups showed that the BF,BV and MTT of HCC region for RFA were significantly different from those of liver tissue near the ablation region,the control group and HCC group(P<0.05).3 Permeability parameters3.1 Results of the parameters of Ktrans(min-1),kep(min-1),ve,vp and HPI of EX:1)HCC region for RFA:0.09±0.07,1.11±0.81,3.94±2.36,0.03±0.03 and 0.82±0.12;2)Liver tissue near the ablation region:0.92±0.58,3.04±1.58,1.38±1.24,0.21±0.14 and 0.27±0.13;3)HCC group and control group:same as the corresponding proportion in Part One;4)Comparison analysis of permeability parameters of ET among groups showed that the kep,ve,vp and HPI of HCC region for RFA were significantly different from those of liver tissue near the ablation region,the control group and HCC group(P<0.05).3.2 Results of the parameters of Ktrans(min-1),kep(min-1),ve,vp,HPI and Fp(ml/min/100g)of EX:1)HCC region for RFA:0.30±0.23,2.77±1.67,0.39±0.29,0.06±0.1 1,0.75±0.24 and 0.25±0.20;2)Liver tissue near the ablation region:2.48±0.73,3.07±1.58,0.73±0.20,0.31±0.15 and 2.32±0.71;3)HCC group and control group:same as the corresponding proportion in Part One;4)Comparison analysis of permeability parameters of EX among groups showed that the Ktrans,ve,vp,HPI and Fp of HCC region for RFA were significantly different from those of liver tissue near the ablation region(P<0.05),while kep showed no significant difference between the two groups(P=0.4046).Ktrans,ve,vp,HPI and Fp of HCC region for RFA were significantly different from those of control group(P<0.05),while kep showed no significant difference between the two groups(P=0.9348).4 Comparison of the parameters between ET and EX within groups.Within HCC region for RFA,Krans,kep and ve showed significant difference between two models(P<0.05),while vp and HPI showed no significant difference(P=0.9462 and P=0.0589,respectively).Within liver tissue near the ablation region,Ktrans,ve,vp and HPI showed significant difference between two models(P<0.05),while kep showed no significant difference(P=0.7447).Within HCC region for RFA and liver tissue near the ablation region,there was a certain correlation between the corresponding parameters of the two models:Krans,kep,vp and HPI showed weak to moderate correlation within HCC region for RFA,with r ranging from 0.5926 to 0.7811,while the correlation of ve showed no statistical significance(r/P,0.1489/0.3468,P>0.05);Ktrans kep,ve,vp and HPI showed weak to moderate correlation within liver tissue near the ablation region,with r ranging from 0.3407 to 0.5712,while the correlation of Ktrans and vp showed no statistical significance(r/P,0.1802/0.2534,P>0.05,and r/P,0.3011/0.0526,P>0.05).Results in the incomplete ablation group after RFA1 Results of semi-quantitative parameters TTP(min),MC(mmol/L),IAUC(mmol*min)and MS are as follows:1)Residual tissue:0.83±0.24,1.64±1.27,1.91±1.35 and 5.80±4.34;2)RFA regions:1.22±0.39,0.24±0.13,0.24±0.17 and 0.86±0.45;3)HCC group and control group:same as the corresponding proportion in Part One;4)Comparative analysis of semi-quantitative parameters among groups:incomplete ablation group was significantly different from RFA regions in TTP,MC,IAUC and MS(P<0.05),was significantly different from HCC group in MC,IAUC and MS(P<0.05)but not in TTP(P>0.05),and was significantly different from control group in MC,IAUC and MS(P<0.05)but not in TTP(P>0.05).2 Results of perfusion parameters BF(ml/min/100g),BV(ml/100g)and MTT(min)are as follows:1)Incomplete ablation group:263.17±157.76,43.88±19.90 and 0.24±0.12;2)RFA regions:16.74±10.21,4.00±1.24 and 1.50±0.10;3)HCC group and control group:same as the corresponding proportion in Part One;4)Comparison analysis of perfusion parameters among different groups:incomplete ablation group was significantly different from RFA regions in BF,BV and MTT(P<0.05),was not significantly different from HCC group in BF,BV and MTT(P>0.05),and was not significantly different from control group in BF and BV(P>0.05).3 Permeability parameters3.1 Results of the parameters Ktrans(min-1),kep(min-1),ve,vp and HPI of ET are as followed:1)Residual tissue:1.54±0.83,3.90±1.96,1.36±1.06,0.35±0.22 and 0.68±0.18;2)RFA regions:0.09±0.06,1.06±0.89,4.36±2.60,0.04±0.03 and 0.81±0.14;3)HCC group and control group:same as the corresponding proportion in Part One;4)Comparative analysis of permeability parameters ET among different groups:Incomplete ablation group was significantly different from RFA regions in kep,ve,vp and HPI(P<0.05),was not significantly different from HCC group in kep,v.,vp and HPI(P>0.05),was significantly different from control group in Ktrans,kep,vp and HPI(P<0.05)but not in vp(P=0.7143).3.2 Results of the parameters Ktrans(min-1),kep(min-1),ve,vp,HPI and Fp(ml/min/100g)of EX are as follows:1)Residual tissue:2.03±0.75,1.88±1.40,0.81±0.20,0.35±0.21,0.55±0.29,and 1.95±0.76;2)RFA regions:0.32±0.25,2.41 ±1.56,0.44±0.29,0.07±0.13,0.73±0.27 and 0.26±0.21;3)HCC group and control group:same as the corresponding proportion in Part One;4)Comparative analysis of permeability parameters of EX among different groups:Residual tissue was significantly different from RFA regions in Ktrans,ve,vp,HPI and Fp(P<0.05)but not in kep(P=0.1391),was not significantly different from HCC group in each parameter(P>0.05),and was significantly different from control group in Ktrans kep,ve,vp and HPI(P<0.05)but not in r of Fp(P=0.0777).4 Difference tests of the same parameters between ET and EX within groups:Within incomplete ablation group,Ktrans,ve,kep and HPI showed significant difference between the two models(P<0.05);within RFA regions,Ktrans,kep and ve showed significant difference between the two models(P<0.05),while vp and HPI showed no significant difference(P=0.9551 and P=0.0583,respectively).In incomplete ablation,the correlation coefficients of Ktrans,vp and HPI between the two models were 0.3993,0.6136 and 0.8694,respectively(P<0.05),while the correlation coefficients of kep and ve were 0.3939 and 0.5440,respectively,without statical significance(P>0.05).In RFA regions,the correlation coefficients of Ktrans,kep,ve and HPI between the two models were 0.5931,0.7644,0.6626 and 0.7729,respectively(P<0.05),while the correlation coefficients of vp was 0.7447,without statical significance(P>0.05).Conclusions1 Analysis of semi-quantitative parameters,perfusion parameters and permeability parameters of DCE-MRI can indicate the microcirculation function changes in ablation focus,tumor residual lesions and normal liver tissue after HCC RFA.2 Multi-parameter DCE-MRI combined with pharmacokinetic model can quantitatively assess the efficacy of HCC RFA,strengthen the objectivity of efficacy assessment,and is a significant supplement to the morphological and anatomical evaluation of conventional MRI.Conclusions of the paper1 DCE-MRI combined with the semi-quantitative parameters,perfusion parameters and permeability parameters obtained from the pharmacokinetic model can provide quantitative information of HCC microcirculation,which is of great value in evaluating the pathophysiological characteristics of HCC.2 Both ET and EX as pharmacokinetic permeability models have ideal diagnostic efficacy in HCC evaluation,and EX is more comprehensive in evaluation.3 Analysis of semi-quantitative parameters,perfusion parameters and permeability parameters of DCE-MRI indicates the microcirculation function changes in ablation focus,tumor residual lesions and normal liver tissue after RFA for HCC4 Multi-parameter DCE-MRI combined with pharmacokinetic model can provide more abundant and accurate information about the tissue microcirculation changes for the diagnosis and the RFA efficacy assessment of HCC,and is also a significant and valuable supplement to the morphology and anatomy of conventional MRI.5 Supports from multicenter bigdata is still necessary to formulate the scanning plan and evaluation criteria of DCE-MRI in the evaluation of HCC and its RFA efficacy. |
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