The Feasibility Of Multi-parametric Multi-ti Arterial Spin-labeling In Astrocytomas

Part ? Review The Application of Arterial Spin-Labeling in CNS NeoplasmBrain tumor is one of most common diseases threatening people's normal life.Medical imaging examination is essectial for the clinical diagnosis and treatment of brain tumor disease.Tissue perfusion is a fundamental physiological parameter that is closely linked to tissue function,and disorders of perfusion are leading causes of medical morbidity and mortality.The role of neuroimaging in patients with brain tumors is no longer simply to evaluate anatomical localisation and morphological modification.Among functional techniques,perfusion imaging,that proposes to measure the degree of tumor angiogenesis,is an important marker,particularly in gliomas.The main imaging techniques evaluating hemodynamics including nuclear medicine,such as PET,and also Xe-CT,dynamic perfusion computed tomography(PCT),perfusion weighted imaging(PWI)and so on.There two most common methods for measuring perfusion with MRI including dynamic susceptibility contrast(DSC)which is more acceptable,and arterial spin-labeling(ASL).Although clinical experience to date is much more extensive with DSC perfusion MRI,ASL methods offer several advantages.In arterial spin-labeling MRI,the tracer is a magnetic label applied to the water molecules of flowing blood.Typically the magnetic label is produced by saturating or inverting the longitudinal component of the MR signal.Once in the capillaries,the tagged water passes into brain tissue,where it alters the local tissue's longitudinal magnetization.The primary advantages of ASL are that completely noninvasive absolute cerebral blood flow(CBF)measurements are possible with relative insensitivity to permeability,and that multiple repeated measurements can be obtained to evaluate one or more interventions.ASL perfusion methods have been applied in many clinical settings,including acute and chronic cerebrovascular disease,CNS neoplasms,epilepsy,aging and development,neurodegenerative disorders,and neuropsychiatric diseases.Although ASL MRI can be carried out in any organ,most studies to date have focused on the brain.The present.review focuses on ASL perfusion MRI and applications in CNS neoplasms.Part ? The Feasibility of Multi-Parametric Multi-TI Arterial Spin-Labeling MRI in Astrocytomas:Comparison with Dynamic Susceptibility Contrast ImagingBackground and objectivesGlial tumors commonly occur in brain of adults,and histopathological distribution of gliomas was complex between low grade and high grade.The clinical manifestation and therapeutic schemes for different malignancies are totally different.MRI is the most common imaging strategy for evaluating tumors.Perfusion imaging in brain tumors has important clinical and diagnostic implications.DSC is kind of relative traditional and widely accepted perfusion method.Arterial spin-labeling(ASL)was characterized as a reliable alternative by taking proton in arterial blood as intrinsic tracer compared to invasive measurement techniques.The new ASL method with multiple inversion time(mTI-ASL)allows assessment of ASL time series at multiple increment times with analysis of the bolus arrival time(BAT)and corrected CBF.The study aimed to evaluate the reliability and utility of mTI-ASL and especially the new parameter BAT by comparing it with DSC parameters in astrocytomas.Materials and Methods1.Subjects:In the first session,we supposed to evaluate the test-retest variability(TRV)of CBF-mTI and BAT parameters derived from mTI-ASL.Ten healthy volunteers(male:n=7,female:n = 3,mean age 52 years,age range from 21 to 65 years)underwent two totally the same mTI-ASL scans within 24 hours.One sagittal T1-weighted imaging 3D-MPRAGE(3-dimensional magnetization-prepared rapid gradient echo)scan was executed during the time lag of 30 minutes between two mTI-ASL scans.In the second session about the correlation analysis between mTI-ASL and DSC,24 patients(13 male,mean age 55 years,age range 16-70 years)suffering astrocytomas were recruited,including glioblastomas(World Health Organization[WHO]?,n = 7),anaplastic astrocytomas(WHO ?,n = 8),diffuse astrocytomas(WHO ?,n = 9).All the lesions were histopathologically proved.2.MR imaging:All data were collected on a 3.0T MR scanner(Magnetom Skyra,Erlangen,Germany)using 32-channel head coil.In the first session,healthy volunteers underwent two totally the same mTI-ASL scans within 24 hours and one sagittal T1-weighted imaging 3D-MPRAGE between two mTI-ASL scans.In the second session,subjects with astrocytomas underwent axial T2-weighted TSE imaging,axial T1-weighted TSE sequence,mTI-ASL and DSC scans.We used a pulsed ASL sequence with flow-sensitive alternating inversion recovery labeling and a quantitative imaging of perfusion with a single subtraction with a thin-section TI1 periodic saturation scheme combined with a 3D gradient and spin-echo readout at multiple TIs 16.The sequence was extended to include an MO scan and automated inline processing of the multi-TI data.The Buxton model was fitted with a non-linear fitting algorithm to obtain quantitative CBF and BAT maps.DSC scans were acquired using an EPI sequence with an intravenous bolus injection of gadodiamide(0.1 ml/kg).3.Data process and measurements:The CBF-mTI and BAT maps were automated processed inline from the mTI-ASL data.The CBF-DSC,CBV,MTT and TTP maps derived from DSC-MRI data were manually processed on Siemens workstation by Syngo.via.In the first session of this study,the test-retest variability(TRV)of each voxel was calculated using this equation:200%*(test 1-test 2)/(test 1 + test 2)We used the MRIcron software to draw VOIs and to calculate the average value within each VOI.For each subject,one neuroradiologist draw three VOIs(8-10 voxels)on the solid tumor area and one similarly sized VOI in the contralateral normal-appearing white matter(NAWMc)of the frontal lobe on T2-weighted images.All VOIs were then projected onto the maps derived from ASL and DSC using MRIcron.The absolute perfusion values(marked aCBF-mTI,aBAT,aCBF-DSC,aCBV,aMTT,aTTP)were calculated as the average value of three 8-10-voxel sized VOIs in tumors.The normalized values were obtained by dividing the mean value of the three tumor VOIs by that of the NAWMc VOI for each patient based on previous reports,and were marked as nCBF-mTI,nBAT,nCBF-DSC,nCBV,nMTT and nTTP.In addition to conducting correlation analyses of both the absolute and normalized values between mTI-ASL and DSC-MRI,we also evaluated the signal-to-noise ratio(SNR)of the tumor and NAWMc and the contrast-to-noise ratio(CNR)for the BAT and TTP maps.4.Statistical analysis:We employed the SPSS Version 19.0 for statistical analysis.We performed a volume-based paired t-test analysis(VBA)by SPM8 to evaluate the test-retest variability.Spearman's nonparametric correlation test was performed to detect the parameters,both the absolute and normalized values of mTI-ASL and DSC.The comparison of CNR between BAT and TTP maps was performed by Wilcoxon Sign-Rank tests.Mann-Whitney U test was performed to the comparison between HGG and LGG group in terms of parameters.P<0.05 was defined as statistically significant.ResultsFor the ten volunteers,no significant difference was detected between the two measurements within 24 hours.The TRV was around 10%in most cortex areas.The aCBF-mTI and aCBF-DSC values were significantly correlated(r = 0.605,P=0.002).The aCBV value is significantly correlated with the aCBF-mTI(r = 0.475,P=0.019),aCBF-DSC(r = 0.864,P<0.001),aMTT(r = 0.425,P=0.038).Significant correlation also existed between aBAT and aTTP values(r = 0.43,P = 0.036).There was highly significant correlation between mTI-ASL and DSC normalized ratios of CBF measurements(r = 0.768,P<0.001).The nCBV is significantly correlated with the most numerous parameters,including nCBF-mTI(r = 0.635,P =0.001),nDSC-CBF(r = 0.756,P<0.001),nMTT(r = 0.447,P = 0.029).The mTI-ASL estimation of nBAT was moderately correlated with nTTP(r = 0.483,P =0.017).We performed a calculation about the CNR of BAT and TTP maps.We outlined the whole brain in the plane performing tumor evaluation as background.The SNR and CNR were calculated as follows:SNRtumor = BATtumor(TTPtumor)/SDbg[1]SNRNAWMc = BATNAWMc(TTPNANAWMc)/SDbg[2]CNR(BAT or TTP)= SNRtumor-SNRNAWMc[3]Where BATtumor(TTPtumor)is the absolute value of the tumor in terms of the BAT(TTP);BATNAWMc(TTPNAWMc)is the absolute value of the contralateral normal-appearing white matter in terms of the BAT(TTP);SDbg is the standard deviation of the background signal intensity.The CNR of the BAT map was significantly higher than that of the TTP map(median,range:0.69,0.06-1.36 vs.0.10,0.01-1.10,P<0.001).Here,we also compared both absolute and normalized parameters between mTI-ASL and DSC in differentiating HGG and LGG grades.There was significant difference for nCBF-mTI(18.24,5.80-67.56 vs 6.66,3.05-14.65,P = 0.008),nBAT(0.67,0.40-1.57 vs 1.26,0.83-1.66,P = 0.005),nCBF-DSC(6.20,0.74-11.82 vs 1.26,0.72-7.24,P = 0.007),nCBV(7.01,2.95-15.70 vs 1.61,0.71-8.52,P =0.012),but was no for nMTT(P = 0.523)and nTTP(P = 0.474)in the comparison between HGG and LGG groups.For absolute values,significant difference was detected only in aCBF-DSC(413.61,192.91-683.53 vs 96.47,41.96-425.53,P = 0.001)and aCBV(92.7,39.21-209.76 vs 29.57,7.93-140.70,P = 0.015)between HGG and LGG groups.There was also no significant difference for aMTT(P = 0.814)and aTTP(P =0.790)in the comparison between HGG and LGG groups.Compared to the normalized form,aCBF-mTI(P = 0.087)and aBAT(P = 0.367)were both invalid in HGG and LGG discrimination.ConclusionIn this study we used the mTI-ASL perfusion imaging,which allows the contrast-free assessment of BAT and CBF in brain tumors.The correlation coefficients of parameters between mTI-ASL and DSC were higher in normalized form compared with the absolute values,BAT was significantly correlated with TTP.In a word,mTI-ASL,especially the BAT as a relative new parameter which can detect temporal dynamics,were reliable in evaluating the perfusion of brain tumors.Part ? Improving the Grading Accuracy of Astrocytic Neoplasms Noninvasively by Combining Timing Information with Cerebral Blood Flow:A Multi-TI Arterial Spin-Labeling MR Imaging StudyBackgrounds and objectivesHistopathological grading of brain tumors which is achieved by surgical excision or stereotactic biopsy is crucial for optimal treatment planning.Conventional CT and MRI techniques are limited in grading central nervous system(CNS)neoplasms and assessing extent of infiltration and treatment responseor effects.Findings from conventional imaging studies can suggest aggressive tumor behavior,including enhancement,ill-defined borders,necrosis and so on.However,such findings are often not specific;for example,while enhancement tends to suggest a higher-grade neoplasm,it is neither sensitive nor specific in this regard.High-grade neoplasms may show little or no enhancement,while low-grade neoplasms may demonstrate intense enhancement.In the study,we aimed to test the performance abilities of different perfusion parameters obtained from multi-TI arterial spin-labeling(mTI-ASL),single-TI ASL(sTI-ASL)and other conventional MRI modalities at grading astrocytic neoplasms and investigate the value of mTI-ASL method in improving diagnostic accuracy.Materials and methods1.Subjects:Forty-three patients(21 males,mean age:51 years,range:15-73 years)with new-onset astrocytomas were consecutively included.Patients were histologically calssified for three grades:glioblastomas(n = 13,World Health Organization[WHO]IV),anaplastic astrocytomas(n = 15,WHO III),and diffuse astrocytomas(n = 15,WHO II).2.MR imaging:All data were collected on a 3.0T MR scanner(Magnetom Skyra,Siemens,Erlangen,Germany)using 32-channel head coil.The standard MRI protocol consisted of axial T2-weighted TSE sequence,T1-weighted TSE sequence,contrast-enhanced T1-weighted images and mTI-ASL sequence.The parameters were the same with part ?.3.Data process and measurements:The conventional MR features were scored by two neuroradiologists with more than 10 years of experience.The mean of the summed scores from the two observers for the MR features of each patient were used for the analyses.Instead of executing one conventional sTI-ASL sequence,we only selected the perfusion-weighted images from a single TI(TI = 1920 ms)to measure the normalized CBF of sTI-ASL(nCBF-sTI).The measurement of mTI-ASL and sTI-ASL was performed using volume of interest(VOI)analysis by two experienced neuroradiologists by using MRIcron software and obtained the nCBF-mTI,nBAT,nCBF-sTI value by using VOI method just as part II described.The averaged value of two neuroradiologists was used for further analyses.4.Statistical analysis:We used the SPSS Version 19.0 for data analysis statistically.The inter-rater reliability was evaluated using the intraclass correlation coefficient(ICC).We applied Kruskal-Wallis tests for detecting inter-group differences(among the WHO II,WHO III,and WHO IV grades).We employed Mann-Whitney U tests to evaluate the difference between the LGG and HGG groups.Receiver operating characteristic(ROC)curves analyses were performed and also calculated the areas under the ROC curve(AUCs)by using MedCalc12.5.Wilcoxon Sign-Rank tests were employed to evaluate the differences between the nCBF-mTI and nCBF-sTI values.Spearman correlation coefficients were calculated between the nCBF-mTI and nBAT values and between the nCBF-sTI and nBAT values.The diagnostic accuracy percentage of each parameter and the combined parameters were calculated using Fisher's linear classification algorithm in MATLAB.Results1.The sum of scores(P = 0.006),nCBF-sTI(P = 0.003),nCBF-mTI(P<0.001),and nBAT(P = 0.002)could all independently differentiate LGGs from HGGs.When comparing between two grades,significant differences were detected by the sum of scores(P = 0.015)only between the WHO II and ? grades.Significant differences in terms of the nCBF-mTI values were detected between the WHO II and WHO III grade groups(P = 0.021),WHO II and WHO ? grade groups(P<0.001),and between WHO III and WHO IV grade groups(P = 0.023).The nBAT values of the WHO II and WHO III grade groups were significantly different(P = 0.005),but no significant difference was detected between grade pairs.For the nCBF-sTI values,a significant difference was only detected between the WHO ? and ? groups(P ?0.006).2.The nCBF-mTI value was higher than the nCBF-sTI value.We employed Wilcoxon Sign-Rank test to examine this difference.When all patients were treated as one group,the nCBF-mTI and the nCBF-sTI values were significantly different(P =0.012).In HGG grade group,a significant difference was also observed between the nCBF-mTI and nCBF-sTI values(P = 0.023),but a difference was not identified between these values in LGG patients.The nCBF-mTI value was non-significantly higher than nCBF-sTI value for the separate WHO II,WHO ?,and WHO ? grade groups.Additionally,we found that the nCBF-mTI and nCBF-sTI values increased as the tumor malignancy grade increased,while the nBAT values demonstrated the opposite trend.The nBAT value was negatively correlated with the nCBF-mTI(r =-0.467,P = 0.002)and nCBF-sTI(r =-0.302,P = 0.049)values.3.The sum of scores was able to separate different grades with AUCs of 0.716(WHO ? vs.?),0.805(WHO II vs.IV),0.603(WHO III vs.IV),and 0.757(LGGs vs.HGGs).The nCBF-mTI value showed excellent performances with AUCs of 0.813(WHO ? vs.WHO ?),0.964(WHO II vs.IV),0.872(WHO III vs.IV),and 0.883(LGGs vs.HGGs).The nBAT was able to discriminate the WHO II and III grades with an AUC of 0.836.The nCBF-sTI could only statistically differentiate the WHO? and ? groups(AUC = 0.826).We used the method of Delong et al.for the calculation of the difference between two AUCs.The AUC of nCBF-mTI was higher than that of sum of scores in all inter-group comparisons,but the difference was not significant(all P>0.05).There was no significant difference between any other two AUCs of parameters.4.The diagnostic accuracies analysis shows that the nCBF-mTI value had the best performance,with an accuracy of 65.10%,compared to the sum of scores of conventional MR features(55.80%),nCBF-sTI value(51.20%),and nBAT value(37.20%).Combining the nCBF-mTI and nBAT values effectively improved the diagnostic accuracy to 72.10%which represented the overall efficiency of mTI-ASL,compared to the accuracy obtained using only the nCBF-mTI value(65,10%).The diagnostic accuracy of combining nCBF-sTI and sum of scores was 55.50%.Although it was slightly higher than only using nCBF-sTI,there was no big improvement compared to applying the sum of scores independently.When combining nCBF-mTI,nBAT and sum of scores together,the diagnostic accuracy increased to 81.40%.ConclusionThe nCBF-mTI was superior to conventional MRI features,nCBF-sTI and nBAT for grading WHO ?,WHO ?,and WHO IV astrocytic neoplasms independently.The nBAT reflects the temporal dynamic behavior of astrocytomas and can improve the diagnostic accuracy when combined with the nCBF-mTI.Combining the mTI-ASL with a conventional MR scan can efficiently improve the diagnostic accuracy for grading astrocytomas.