(3.3.2)--脑科学与影像新技术.pdf

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1、RESEARCH ARTICLEOpen AccessGlioma grading by microvascular permeabilityparameters derived from dynamic contrast-enhanced MRI and intratumoral susceptibilitysignal on susceptibility weighted imagingXiaoguang Li1,Yongshan Zhu2,Houyi Kang1,Yulong Zhang1,Huaping Liang3,Sumei Wang4and Weiguo Zhang1,3*Abs

2、tractBackground:Dynamic contrast-enhanced MRI(DCE-MRI)estimates vascular permeability of brain tumors,andsusceptibility-weighted imaging(SWI)may demonstrate tumor vascularity by intratumoral susceptibility signals(ITSS).This study assessed volume transfer constant(Ktrans)accuracy,the volume of extra

3、vascular extracellular space(EES)per unit volume of tissue(Ve)derived from DCE-MRI,and the degree of ITSS in glioma grading.Methods:Thirty-two patients with different glioma grades were enrolled in this retrospective study.Patientsunderwent DCE-MRI and non-contrast enhanced SWI by three-tesla scanni

4、ng.Ktransvalues,Ve,and the degree ofITSS in glioma were compared.Receiver operating characteristic(ROC)curve analysis determined diagnosticperformances of Ktransand Vein glioma grading,and Spearmans correlation analysis determined the associationsbetween Ktrans,Ve,ITSS,and tumor grade.Results:Ktrans

5、and Vevalues were significantly different between low grade gliomas(LGGs)and both high gradegliomas(HGGs)and grade II,III and IV gliomas(P0.01).The degree of ITSS of LGGs was lower than HGGs(P0.01),and the ITSS of grade II gliomas was lower than grade III or IV gliomas.Ktransand Vewere correlated wi

6、th glioma grade(P0.01),while ITSS was moderately correlated(P0.01).Ktransvalues were moderately correlated with ITSS in thesame segments(P0.01).Conclusion:Ktransand Vevalues,and ITSS helped distinguish the differences between LGGs and HGGs andbetween grade II,III and IV gliomas.There was a moderate

7、correlation between Ktransand ITSS in the same tumorsegments.Keywords:Brain tumor,Glioma,Grading,Dynamic contrast-enhanced MRI,Susceptibility weighted imaging,Intratumoral susceptibility signalBackgroundThe angiogenesis of intracranial gliomas plays an import-ant role in evaluating the biological ac

8、tivity and malig-nancy of a tumor.Tumor vascularity is mostly immatureneovascularity consisting of endothelial cells and basementmembranes with incomplete structures,resulting in anincrease in microvascular permeability.The degree of thisincrease is associated with tumor type and the degree ofmalign

9、ancy.Moreover,angiogenesis are prone to bleeding,and advanced tumors are inclined to have more angiogen-esis and the increased formation of micro-hemorrhage1-3.Currently,DCE-MRI may provide informationabout neovascularity and angiogenesis in gliomas mainlythrough two important quantitative parameter

10、s,Ktransand Ve4,5.Ktransis the volume transfer constant inunit time for the transfer of contrast medium from thevessel into the EES,which reflects the intratumoralmicrovascular permeability.Veis the volume fraction*Correspondence:1Department of Radiology,Institute of Surgery Research,Daping Hospital

11、,Third Military Medical University,Chongqing 400042,China3State key laboratory of Trauma,Burns and Combined Injury,Institute ofSurgery Research,Daping Hospital,Third Military Medical University,No.10,Changjiang Zhilu,Da Ping,Yuzhong Distriction,Chongqing 400042,ChinaFull list of author information i

12、s available at the end of the article 2015 Li et al.;licensee BioMed Central.This is an Open Access article distributed under the terms of the Creative CommonsAttribution License(http:/creativecommons.org/licenses/by/4.0),which permits unrestricted use,distribution,andreproduction in any medium,prov

13、ided the original work is properly credited.The Creative Commons Public DomainDedication waiver(http:/creativecommons.org/publicdomain/zero/1.0/)applies to the data made available in this article,unless otherwise stated.Li et al.Cancer Imaging (2015)15:4 DOI 10.1186/s40644-015-0039-zof contrast medi

14、um leaking into the EES.SWI is ex-tremely sensitive to the vascular structures and bloodmetabolites.Researchers have found that parametersassociated with DCE-MRI and the degree and distribu-tion of ITSS are significantly correlated with the gradesof gliomas 6-10.These two methods can reveal thepatho

15、physiological state of glioma microvessels fromdifferent angles.Therefore,in the present study,it wasinferred that a large number of angiogenesis with im-perfect functions may reside within the ITSS regionsand that ITSS grades may excellently correspond withthe maximal Ktransvalue,so these two param

16、eters wereboth applied to diagnose glioma grades.In the presentstudy,these two methods were applied to assess gliomas,to evaluate the accuracy and value of the associated pa-rameters in diagnosing the grades of gliomas,and toanalyze the correlation between the Ktransvalue and ITSSin the same tumor s

17、ection as well as the relations betweenthese two parameters and microvessel density(MVD)andvessel diameter(VD).MethodsPatient selection and histopathological diagnosisThis retrospective study was approved by the institu-tional review board of our hospital group.All patientswere scanned for preoperat

18、ive assessment,and informedconsent was obtained from each patient.MR examina-tions of 32 patients(17 female and 15 male,aged 12-69years old,mean age 42.6 14.3 years old),including 15patients with LGGs(7 astrocytomas,6 oligodendrogli-omas,and 2 oligoastrocytomas)and 17 patients withHGGs(3 anaplastic

19、astrocytomas,3 anaplastic oligo-dendrogliomas,2 anaplastic oligoastrocytomas,and 9glioblastomas),were reviewed.All patients underwentconventional MRI,DCE-MRI,and SWI before surgicalresection.The pathologic specimens were classifiedusing the 2007 World Health Organization classificationcriteria for g

20、lioma after craniotomy and tumor total re-section 11.Imaging protocolAll MR imaging was performed using a 3.0 T MR system(Magnetom Verio,Siemens Medical Solutions,Erlangen,Germany)with an 8-element head matrix coil.The con-ventional MRI included axial and sagittal T1-weighted,T2-weighted,and axial f

21、luid-attenuated inversion recov-ery(FLAIR)sequences.DCE-MRI was performed using the sequences describedbelow.First,a baseline T1-weighted MRI(TR/TE=5.08/1.74 ms,FOV=260 mm260 mm,matrix=138192,slice-thickness=5 mm,and flip-angles of 2 and 15)wasused to create two precontrast datasets.Then,a DCEperfus

22、ion imaging dynamic series was performed usinga T1-twist sequence with a flip angle of 12(TR/TE=4.82/1.88ms,FOV=260mm 260mm,matrix=138 192,slice thickness=3.6 mm),which was com-prised of 70 measurements with a temporal spacing ofapproximately 8 s.At the beginning of the baseline acqui-sition,a bolus

23、 of 0.1 mmol/kg gadolinium(Gd)-DTPAcontrast agent(Omniscan,GE Healthcare,Shanghai,China)was injected intravenously at a rate of 4 ml/s.SWI was performed using a 3D fully flow-compensatedgradient-echo sequence,and the detailed parameters wereas follows:TR/TE=28.0/20.0 ms,flip angle=15,FOV=230 mm230 m

24、m,FOV phase=75%,SNR=1.00,slicethickness=1.2 mm,total acquisition time=5 min and 5 s,voxel size=0.80.71.2 mm.Image analysisQuantitative analysis of DCE imagesKtransand Vevalues were estimated using Tissue-4Dsoftware in a Siemens Syngo MR workplace,which wasbased on the two-compartment pharmacokinetic

25、 modelby Tofts and Kermode 12.Ktransand Vemeasurementswere acquired by simultaneous observation of axial post-contrast T1-weighted MRI and corresponding KtransandVemaps.The ROI(region of interest)was selected fromthe axial post-contrast T1-weighted images and thenautomatically transformed into the c

26、orresponding para-metric maps.For each tumor,3-5 ROIs of 40-60 mm2were manually positioned on the corresponding slices ofKtransand Vemaps by an experienced radiologist.Selec-tions of ROIs within the tumor zone were continued un-less a maximal Ktransvalue inside an ROI was acquired.To avoid necrotic,

27、cystic,and hemorrhagic regions,ROIselection was based on enhanced T1-weighted images.Semi-quantitative analysis of SWI imagesThe degree of ITSS within tumors included 4 grades ac-cording to the methods described in a previous reviewby Park et al.10,No ITSS represented grade 0,1-5 dot-like or fine li

28、near ITSS represented grade I,6-10 dot-likeor fine linear ITSS represented grade II,and11 dot-likeor fine linear ITSS in the continuous region representedgrade III.To observe the corresponding relations betweenmaximal Ktransvalue areas and areas with the mostdensely prominent ITSS,Ktransand SWI imag

29、es were co-registered using Image Pro Plus 6.0(Media Cybernetics,Inc.USA).Measurements of mean MVD and VD valuesThe MVD and VD of the surgical specimens immuno-histochemically stained with anti-CD34 were evaluated.The measurements of the mean MVD and VD valueswere attained using a computer-assisted

30、image analysissystem(Leica,Olympus,Italy).The counting methoddescribed by Weidner et al.13 was adopted for theevaluation of MVD.Then,at least 5 transversallyLi et al.Cancer Imaging (2015)15:4 Page 2 of 9sectioned vessel sections with a single layer of endothe-lial cells were chosen for each hotspot

31、with or withoutthe thin basement membrane.The mean VD was calcu-lated from the minimum to the maximum diameter ofthose given vessel sections.Statistical analysisStatistical analysis was performed using SPSS software(version 18.0,SPSS Inc.,Chicago,IL,USA).All datawere expressed as the mean standard d

32、eviation(SD).Analysis of variance(ANOVA)was used to compare thevalues of Ktrans,Ve,MVD,and VD.The Kruskal-Wallistest was executed to compare ITSS degrees among dif-ferent grades of gliomas.The ROC curve analysis wasconducted to decide the cut-off value with the diagnosticperformance of Ktransand Vef

33、or glioma grading.Rela-tionships between those parameters such as Ktrans,Ve,degree of ITSS,tumor grade,MVD,and VD were re-spectively analyzed using Spearmans correlation.For allstatisticaltests,P 0.05wasconsideredstatisticallysignificant.ResultsThe effectiveness of Ktransand Vevalues in gliomagradin

34、gThe mean Ktransand Vevalues of LGGs and HGGs areshown in Table 1.It can be seen that the Ktransand Vevalues were significantly higher in HGGs than those inLGGs(P0.01).The mean Ktransand Vevalues of grade IIgliomas were significantly lower than those of grade III orIV gliomas(P0.01).However,no signi

35、ficant differencesin Ktransand Vevalues between grade IV and grade III gli-omas were found(Table 2).Both Ktransand Vevalues werestrongly correlated with glioma grade(r=0.782 and 0.717,respectively,P0.01).The ROC curve analyses of Ktransand Vevalues be-tween different grades of gliomas are shown in T

36、able 3.The cut-off value of Ktrans(0.054 min1)for differenti-ation between LGGs and HGGs provided the best com-bination of sensitivity(94.1%)and specificity(93.3%),and the area under the curve(AUC)of Ktranswas 0.941.The cut-off value of Ve(0.296)provided the best com-bination of sensitivity(92.9%)an

37、d specificity(91.7%),and the AUC of Vewas 0.937.Additionally,the differentcut-off values of Ktransand Vefor differentiation betweengrade II and grade III or IV gliomas also indicated diag-nostic accuracy.The morphology and degree of ITSS among gliomasITSS were seen in 8 of 9 grade IV patients,in all

38、 8 gradeIII patients,and in 11 of 15 grade II patients.The Kruskal-Wallis test results showed that the degree of ITSS of LGGswas significantly lower than that of HGGs(P0.01)(Table 1),and there were significant differences in ITSSdegrees between grade II and grade III or IV(P0.01 andP0.05,respectivel

39、y).However,no statistical differencewas found between grade III and grade IV gliomas(Table 2).Spearmans correlation analysis showed a mod-erate correlation between the degree of ITSS and tumorgrade(r=0.515,P0.01,Table 4).Either no or sporadicdot-like ITSS were found in LGGs(Figure 1c)except forthe d

40、ensely prominent ITSS in the 4 cases of oligodendro-glioma(Figure 2c)and single case of oligoastrocytoma.However,the agglomerated mixed nodular and fine linearITSS were seen frequently in HGGs with the exception ofone glioblastoma(Figures 3c and 4c).The relationship between Ktrans,Ve,and the degree

41、ofITSSKtransvalues were also strongly correlated with Vevalues(r=0.823,P 0.01)and moderately correlated with thedegree of ITSS(r=0.473,p0.01)(Table 4).In LGGs,either no or sporadic dot-like ITSS were observed in theSWI images of the 7 cases of astrocytomas,while signsof intratumoral hypoperfusion we

42、re observed in theKtransmaps.Therefore,these two findings were consist-ent with each other(Figure 1b-c).Of the 6 cases ofoligodendrogliomas,4 had densely prominent ITSS intheir SWI images(1 case of grade 2 and 3 cases of gradeTable 1 The mean Ktrans,Vevalues,MVD,VD values and ITSS grade of different

43、 grades of gliomasTumor gradeKtransmin1VeMVDVD(m)ITSS gradeLGG(grade II)0.026 0.0190.1210.13014.75 4.945.101.081.2grade III0.096 0.0630.4830.22526.84 9.177.931.342.8grade IV0.135 0.0680.5250.18022.79 3.519.831.432.4HGG(grade III and IV)0.117 0.0660.5050.19724.70 6.878.931.662.6NOTEKtransmin1:volume

44、transfer constant,Ve:volume of extravascular extracellular space(EES)per unit volume of tissue,MVD:microvessel density,VD:vessel diameter.Table 2 P values from Ktrans,Ve,MVD,VD and ITSS gradefor differentiation between different gradesGradeKtransVeMVDVDITSS gradeII vs III0.0030.0000.0000.0000.002II

45、vs IV0.0000.0000.0000.0000.032III vs IV0.1140.6180.1720.0040.897LGG vs HGG0.0000.0000.0000.0000.001Li et al.Cancer Imaging (2015)15:4 Page 3 of 93).However,their intratumoral perfusions in the Ktransmaps were not too high(the mean Ktransvalue of the 6cases was 0.043).Thus,in the co-registered image,

46、areasof densely prominent ITSS did not completely corres-pond to the areas of maximal Ktransvalues(Figure 2d).Moreover,a phenomenon of non-correspondence be-tween the areas of most densely prominent ITSS and theareas of maximal Ktransvalues was found in 1 out of 2cases of oligoastrocytomas.In HGGs,t

47、he different quantities and morphologies ofITSS were situated at the center or the inner portion ofthe enhancing rim.In DCE-MRI,the highest value ofKtranswas located at the areas near the enhancing rimonT1-weightedcontrastenhancedimages.Co-registered image of Ktransand SWI confirmed that thenodular

48、or fine linear ITSS areas partly corresponded tothe regions of the highest value of Ktransin the sametumor segment(Figure 3d).Remarkably,there was oneglioblastoma on SWI without any signs of ITSS whichexhibited significantly high vascular permeability(highKtransvalues)on DCE-MRI(Figure 4b-c).The cor

49、relation between MVD/VD and Ktrans/Ve/ITSSEndoscopic observations indicated that in low grade as-trocytomas,their microvascularity was sparse,low inMVD,and small in VD,and their vascular structureswere mostly complete(Figure 1e).In oligodendrogliomasor oligoastrocytomas,more angiogenesis with branch

50、-like vessels and a higher MVD were observed,but theirVD values were also small.In HGGs,significantlyincreased in MVD,vessels with irregular and disorderlystructures,and enlarged VD were observed(Figure 3e).The mean MVD(14.75)and VD(5.10 m)of LGGswere significantly lower than those of HGGs(MVD=24.70