A Multimodality MRI Study Of Treatment Response Assessment In Patients With Glioma

Part 1 Three dimensional pseudo-continuous arterial spin labeling(3D-pcASL)in differentiating tumor progression from treated effects in gliomaPurpose:The differential diagnosis of tumor progression and treatment related changes is challenging in patients with newly diagnosed gliomas who have undergone post-surgery radiotherapy or chemoradiotherapy.The study was to evaluate the role of three dimensional pseudo-continuous arterial spin labeling technique(3D-pcASL)in the discrimination.Materials and methods:Thirty-one patients with histopathologically confirmed glioma who had undergone post-surgery radiotherapy or chemoradiotherapy were retrospectively enrolled.All the patients had newly or enlarged contrast-enhancing lesions during or after the treatment.Follow-up MRI scans including 3D-pcASL and contrast-enhancing sequences were available from all the patients who were classified as having tumor progression or treatment related changes according to the second histopathological or clinic-radiological follow-up evidences.The maximum cerebral blood flow(cerebral blood flow,mCBF)of the lesions,rmCBF_cb(mCBF/average CBF of the cerebellum hemisphere)and rmCBF_wm(mCBF/average CBF of the contralateral normal white matter)were all compared between two groups using t test and Mann-Whitney U test of independent samples.The diagnostic performance of the three CBF metrics was evaluated by using an receiver-operating characteristic curve analysis.Results:The maximum cerebral blood flow(cerebral blood flow,mCBF)of the lesions,and between the two groups were statistically significant(88.00[mean]ml 100g-1 min-1±41.14[stand deviation]vs 43.35 ml 100g-1 min-1 ±2.64,P=0.001;2.43 ± 1.30 vs 1.11±0.26,P<0.001;3.87 ± 1.69 vs 1.95 ± 0.39,P<0.001,respectively).The area under the receiver-operating characteristic curve(AUC)of mCBF,rmCBF_cb and rmCBF_wm between the progression and treated effects didn't reach statistical significance.The AUC,best threshold,sensitivity,specificity and accuracy of mCBF,rmCBF_cb and rmCBF_wm were 0.913,62.89 ml 100 g-1 min-1,73.91%,100%,81%;0.935,1.61,82.61%,100%,87%;0.897,2.69,78.26%,100%,84%,respectively.Conclusions:3D-pcASL may be a useful tool to discriminate tumor progression from treatment related changes in patients of glioma during/after radiotherapy or chemoradiotherapy.The maximum of CBF in the new enhancing or enlarged lesions can be a practical promising biomarker in the differentiation of both entities.Part 2 Differentiation of tumor progression from treated effects in glioma under radiotherapy/chemoradiotherapy:a dynamic contrast enhanced MRI studyPurpose:To investigate the role of three dimensional pseudo-continuous arterial spin labeling technique(3D-pcASL)in differentiating tumor progression from treatment related changes in patients with newly diagnosed gliomas who have undergone post-surgery radiotherapy or chemoradiotherapy.Materials and methods:This study was approved by the institutional review board and written informed consent was obtained from all patients.Twenty-one patients with histopathologically proven glioma who had undergone radiation therapy or chemoradiotherapy were retrospectively included.Pharmacokinetic parameters derived from dynamic contrast-enhanced MR imaging,including Ktrans,Kep,ve and vp,analyzed for newly developed or enlarged enhancing lesions,unpaired t tests were used to compare pharmacokinetic parameters between the tumor progression(n = 16)and treatment related changes(n = 5)groups.And then,receiver operating characteristic curve were utilized to determine the diagnostic performance of the pharmacokinetic parameters.Results:The mean Ktrans and vp were higher in the tumor progression group than in the treatment related changes group(meanKtrans,0.0395 min-1±0.0190[standard deviation]VS 0.0195 min-1 ±0.0100,P=0.038;and mean vp,0.0154 ±0.0077 VS 0.0077±0.004,P=0.047,respectively).The threshold,sensitivity,specificity,accuracy,positive predictive value and negative predictive value of Ktrans and vp in differentiating tumor progression from testament related changes were 0.0289min-1,68.75%,100%,76.19%,100%,50%and 0.0130,56.25%,100%,66.67%,100%,41.67%,respectively.Conclusion:Pharmacokinetic parameters from dynamic contrast-enhanced magnetic resonance imaging,including Ktrans and vp,in the entire newly developed or enlarged enhancing lesion has the potential to objectively differentiating tumor progression from treatment related changes in patients with glioma who have undergone radiation therapy or chemoradiotherapy.Part 3 Evaluation of recurrent high-grade gliomas treated with bevacizumab:a three dimensional pseudo-continuous artery spin labelling studyPurpose:Pseudo-continuous artery spin labelling(pcASL)technique has been proven its value in glioma grading.Yet little is known about its role in prognosis of recurrent gliomas.The aim of this study is to investigate the role of cerebral blood flow(CBF)from 3D fast spin echo(FSE)pcASL sequence in predicting the response of recurrent high-grade gliomas(rHGGs)treated with bevacizumab(BEV).Materials and methods:Sixteen patients with rHGGs who underwent 3D FSE pcASL imaging 1-2 days before(baseline or pre-BEV)and within one month after BEV initiation(post-BEV)were included in the study.The average(aCBF)and maximum(mCBF)cerebral blood flow of the enhancing tumor,their respective normalized values to contralateral normal appearing white matter(rCBF_wm and mCBF_wm)and cerebellum(rCBF_cb and mCBF_cb),and the related changes between baseline and post-BEV were evaluated.Receiver operating characteristic(ROC)curve analysis was utilized to define the optimal cutoff perfusion values for OS and PFS prediction.Results:cuoffs of aCBF(43.72 ml/100g/min)pre-BEV for OS,rCBF_cb(1.09)pre-BEV for PFS and OS,and AaCBF(-0.37)for PFS were found to be statistically significant in survival prediction(P=0.026;0.044,0.046,and 0.048 respectively).Specifically,if aCBF was>43.72(ml/100g/min)at baseline,the median OS was 140 days compared with 404 days when aCBF<43.72(ml/100g/min).The percent changes of aCBF predicted a longer PFS than otherwise,if aCBF decreased no less than 37%post-BEV(267 days vs 116 days,P=0.048).With a threshold value of 1.09,rCBF_cb predicted a longer PFS and OS in 9/16 patients when it was no more than 1.09(251 days vs 112 days for PFS;404 days vs 194 days for OS)(P=0.044,P=0.046).Conclusion:Three dimensional FSE pcASL sequence has the potential to predict the OS and PFS in patients with rHGGs treated with bevacizumab.Average CBF at baseline is a promising imaging biomarker to evaluate the prognosis of recurrent high-grade gliomas.Part 4 A comparison study of two different models in measuring the vascular permeability of recurrent high grade gliomas before and after being treated with BevacizumabObjective:To compare the feasibility of two different models(Patlak model and Extended Tofts-Kety model)for DCE-MRI data analysis in measuring the vascular permeability of recurrent high grade gliomas before and after being treated with Bevacizumab,and find a better one.Materials and Methods:Thirty-four MRI scans were enrolled from 13 patients who had been treated by Bevacizumab(BEV)after being diagnosed as recurrent high-grade gliomas.The 34 scans were divided into BEVO group(10 scans)and BEV1 group(24 scans),before and after BEV treatment,respectively.The DCE-MRI data was obtained via a series of 3D-LAVA sequences with multi-flip angles and one with a multi-phase acquisition method.The regions of interest(ROIs)were placed in all lesions of all slices on color coded Ktrans maps.The parameters of both models(Ktrans and Vp)were all obtained on the same ROIs above.And the maximal median for both parameters of all ROIs in a scan was used for the analysis.In statistics analysis,the Spearman correlation and Wilcoxon signed rank test were used.Results:Ktrans and VP were both closely correlated between the two models in both groups[(BEVO group:correlation coefficient,0.915,1;P<0.001for both)(BEV1 group:correlation coefficient,0.818,0.955;P<0.001 for both)].In the BEVO group,Ktrans in the Patlak model was significantly lower than that in the ETK model[median,range:(0.0795,0.0217-0.4479)vs(0.0947,0.0368-0.4883);P=0.013<0.05],so is Vp[(0.0307,0.0062-0.1272)vs(0.0430,0.0091-0.1549);P<0.001],In the BEV1 group,there was no significant difference inKtrans between both models[(0.0535,0.0088-0.2087)vs(0.0563,0,0029-0.3320);P=0.886>0.05].While Vp in the Patlak model was still lower than that in the ETK model[(0.0166,0.0032-0.1088)vs(0.0273,0.0013-0.1523);P<0.001],Conclusion:Although both models can be used,the ETK model is preferable to determine the vascular permeability of recurrent high grade gliomas before and after being treated with Bevacizumab.