Application Of 3D Amide Proton Transfer Weighted Imaging Combined With 3D-pCASL Imaging In Glioma

Glioma is a kind of tumor originating from glial cells.It mainly comes from astrocyte,oligodendrocytes and other glial cells.This kind of tumor is the most common primary brain tumor in adult intracranial,accounting for 50%-60%of primary intracranial tumors.According to the 2016 World Health Organization(WHO)classification of central nervous system tumors,the treatment methods and prognosis of glioma may differ for different glioma grades and isocitrate dehydrogenase(IDH)mutation statuses.Therefore,predicting the grading and IDH mutation status of glioma before surgery is clinically important.Currently,the preoperative diagnosis of glioma mainly depends on tissue biopsy or intraoperative histopathological examination.However,due to the limitations of tissue sampling and the heterogeneity of glioma,the sample tissue does not necessarily represent the most malignant part of tumor tissue,which may underestimate the grade of glioma,mislead clinicians to adopt inappropriate or conservative treatment plans,and affect the prognosis of patients.According to the 2016 WHO classification of central nervous system tumors,high-grade gliomas(WHO Ⅲ or Ⅳ grade)have a high degree of malignancy and a poor prognosis.Currently,the best treatment protocol for high-grade glioma in the world is surgical resection the tumor in the maximum safe range,and use radiotherapy and chemotherapy to prolong the survival period and improve the prognosis.However,due to the infiltrative growth of high-grade glioma and unclear tumor boundary,surgery is often difficult to completely remove the tumor,thus the tumor is easy to recur after surgery.The fatal feature leads to poor prognosis of patients,which seriously affects the survival of patients.Therefore,monitoring the prognosis of patients dynamically and judging whether the tumor has recurred has important clinical value for clinicians to formulate the next treatment plan.Magnetic resonance imaging(MRI)is one of the important means for preoperative classification of glioma or follow-up after surgery and radiotherapy,which has an important impact on the clinicians’ treatment protocol.In the past,gadolinium(Gd)contrast enhancement was considered to be an important sign of high-grade glioma or tumor recurrence.However,the specificity of this sign is not high,and it may be misdiagnosed high-grade glioma or radiotherapy reaction as low-grade glioma or tumor recurrence.With the progress of MRI examination technology,dynamic susceptibility contrast(DSC)perfusion imaging and dynamic contrast enhanced(DCE)imaging based on Gd contrast agent are gradually applied in clinic,and showed broad application prospects in the diagnosis and treatment of glioma.However,the use of Gd contrast agent may increase the risk of nephrogenic systemic fibrosis and deposition in normal brain.For patients who cannot tolerate the contrast agent,children or patients who need repeated examinations,the clinical application is limited sometimes.Therefore,contrast agent-free MRI sequences have some advantages over Gd-enhanced MRI sequences for grading gliomas before surgery.3D Amide Proton Transfer weighted(3D-APTW)is a new technology that does not need contrast agents.While conventional MRI relies on the behavior of water protons in tissue,APTW imaging uses the signal of amide protons(-NH)contained in proteins and peptides.Due to its unique ability,APTW imaging can evaluate the endogenous proteins or polypeptides produced by the proliferation of tissues and cells,and indirectly become an image marker to reflect the proliferation of cells,while cell proliferation is a marker of tumor activity.Therefore,3D-APTW imaging has broad application prospects in the classification of glioma or monitoring the prognosis.Compared to the previous 2D-APTW examination technology that only scans one layer and requires third-party software post-processing,3D-APTW imaging is capable of whole-tumour coverage within a reasonable acquisition time and supports easy viewing by using a rainbow colour scale.As a fast and clinically feasible sequence,determining whether 3D-APTW imaging can be used to aid diagnosis and treatment of glioma is of clinical importance.In the first part of this paper,we studied the application value of clinical type 3D-APTW imaging in predicting the grading of glioma and IDH classification.Research shows that 3D-APTW imaging not only has high diagnostic efficiency in predicting high-and low-grade gliomas and IDH classification,but also can further distinguish different grades of gliomas(WHO Ⅱ,Ⅲ and Ⅳ);In addition,3D-APTW imaging can also be compatible and complementary with 3D pseudocontinuous arterial spin labelling(3D-pCASL)imaging.Combining the two examination can further improve the diagnostic ability of 3D-PCASL imaging to predict the preoperative classification of glioma,and provide imaging basis for the formulation of preoperative diagnosis and treatment protocol for patients with glioma.But this is only the first step in the clinical management of glioma.As is well known,high-grade gliomas are prone to recurrence after surgery.In the process of monitoring the postoperative treatment effect of high-grade glioma,timely judgment of tumor recurrence and adjustment of treatment protocol are important conditions for prolonging patient survival.The second step in the clinical management of glioma after surgery is how to identify the true progress and treatment response of the tumor and then adjustment of treatment protocol.Therefore,the second part of this paper studied the application value of 3D-APTW imaging in identifying the true progression and treatment response of high-grade glioma after surgery.Our study proved that 3D-APTW imaging can non-invasively identify the true progression and treatment response of high-grade glioma after treatment,and has higher differentiation ability than 3D-pCASL imaging;The combination of these two MRI techniques further improve the ability of differential diagnosis and provide imaging interpretation basis for the precise treatment of high-grade glioma patients after surgery.Finally,in the third part of this paper,we reviewed the application progress of APTW in the clinical diagnosis and treatment of glioma,providing reference for related clinical work.Part Ⅰ Application value of 3D amide proton transfer weighted imaging and 3D pseudo-continuous arterial spin labeling imaging in predicting the grade and IDH classification of gliomaPurpose:The goal of this study was to evaluate the diagnostic performance of 3D-APTW imaging and 3D-pCASL alone and in combination in grading gliomas and correlating IDH mutation status.Methods:Preoperatively,81 patients with pathologically confirmed gliomas underwent 3.0-T MRI examinations.Approximately 3-5 circular ROIs of equal area(20 mm2 each)were carefully placed in the solid component of the tumour to include the area with the highest APTW or CBF signal as determined by visual inspection of the APTW or CBF images by two experienced neuroradiologists who were blinded to the histopathological data.The APTW,relative APTW(rAPTW),cerebral blood flow(CBF)and relative CBF(rCBF)were calculated to evaluate in the solid components of the tumours.SPSS 20.0 and MedCalc were used for statistical analysis.The interobserver agreement for all measured values between two observers was analysed by calculating the intraclass correlation coefficient(ICC),and values>0.75 were considered to indicate a good correlation.The APTW,rAPTW,CBF,and rCBF values are expressed as the mean ± standard deviation(SD).Differences between the low grade gliomas(LGG)vs.high grade gliomas(HGG)groups and between the IDH-mut vs.IDH-wt groups were evaluated for all parameters using an independent-samples t test.The tumour and CNAWM or CNAGM parameters were compared using a paired-samples t test for each group.A p value<0.05 was considered statistically significant.Furthermore,the parameters of grade Ⅱ,Ⅲ,and Ⅳ gliomas were compared by one-way analysis of variance(ANOVA).When the variance was assumed to be equal,Bonferroni’s t test was used,and Bonferroni correction was applied for multiple comparisons.The receiver operating characteristic(ROC)curves of each parameter and the curve of the combination of the rAPTW value and rCBF were used to evaluate the ability to grade gliomas and predict IDH mutation status.The cut-off value,sensitivity,specificity,and area under the ROC curve(AUC)were calculated.Results:Patients with HGG showed significantly higher APTW,rAPTW,CBF,and rCBF values than those with LGG(all p<0.001).The APTW and CBF values of the solid part of the tumour were significantly higher than the corresponding parameters of the contralateral normal brain tissue.In the ROC curve analysis,the AUC of rAPTW was the highest at 0.90,and its sensitivity and specificity were 85.4%and 84.8%,respectively;The AUC,sensitivity and specificity of rCBF were 0.84,77.1%and 81.8%,respectively.By adding the rAPTW signal to the rCBF values,the diagnostic ability of the combined parameters improved from 0.84 to 0.96.The APTW,rAPTW,CBF and rCBF values of grade Ⅲ and Ⅳ gliomas were significantly higher than those of grade Ⅱ gliomas;The APTW,rAPTW and rCBF values of grade Ⅲ glioma were significantly lower than those of grade Ⅳ glioma(p<0.01);However,there was no significant difference in CBF between grade Ⅲ glioma and grade Ⅳ glioma(p=0.110).The rAPTW value yielded the highest AUC(0.92)in correlating the IDH mutation status,and the diagnostic ability improved to 0.96 by adding it to the rCBF value.Conclusion:3D-APTW imaging not only has high diagnostic efficiency in predicting LGG vs.HGG and IDH classification,but also can further distinguish different grades(WHO Ⅱ,Ⅲ and Ⅳ)of glioma;compared with 3D-pCASL imaging,it has higher diagnostic performance;In addition,3D-APTW imaging can also be compatible and complementary with 3D-pCASL imaging.Combining the two can further improve the diagnostic ability of 3D-pCASL imaging to predict the preoperative classification of glioma.Part Ⅱ Diagnostic value of 3D amide proton transfer weighted imaging in differentiating true progression and treatment response after treatment in high-grade glioma:comparison with 3D-pCASL and DWI imagingPurpose:To assess and compare the diagnostic performance of 3D-APTW imaging,3D-PcASL imaging and diffusion-weighted imaging(DWI)in distinguishing tumor progression(TP)from treatment response(TR)in posttreatment malignant glioma patientsMethods:Forty-eight patients with suspected tumor progression were prospectively enrolled.Histological or longitudinal routine MRI follow-up over six months was assessed to confirm lesion type.Approximately 3-5 circular ROIs of equal area(20 mm2 each)were carefully placed in the Gd-enhancing area to include the area with the highest APTW and CBF signal and the lowest ADC signal respectively as determined by visual inspection of the APTW,CBF or ADC images by two experienced neuroradiologists who were blinded to the Follow up results.SPSS 20.0,MedCalc and GraphPad Prism were used for statistical analysis.The interobserver agreement for all measured values between two observers was analysed by calculating the intraclass correlation coefficient(ICC),and values>0.75 were considered to indicate a good correlation.Each MRI value was expressed as the mean ± standard deviation.MRI parameters between the TP and TR groups were compared by independent sample t tests,p<0.05 was considered statistically significant..The ROC curves of each parameter and that of the combination of rAPTW and rCBF were used to evaluate the performance in differentiating between TR and TP.The cutoff value,sensitivity,specificity,and area under the curve(AUC)were calculated.Results:The TP group showed a significantly higher rAPTW and rCBF than those in TR group,Wherein the rAPTW value has higher discrimination performance;the AUC of rAPTW to distinguish between TP and TR was 0.911,with a sensitivity of 90.3%,a specificity of 82.4%and the optimal cut-off value of 2.25.The AUC of rCBF to distinguish between TP and TR was 0.852,with a sensitivity of 80.6%,a specificity of 82.4%and the optimal cut-off value of 1.41 respectively.By adding the rAPTW signal to rCBF values,the diagnostic ability was improved from 0.852 to 0.951.However,ADC showed no significant differences between the TP and TR groups,with an AUC lower than 0.70.Conclusion:Both 3D-PcASL and 3D-APTW imaging could distinguish TP from TR,and 3D-APTW had a better diagnostic performance.However,ADC showed no significant differences between the TP and TR groups.Combining the rAPTW signal and rCBF values could further improve the diagnostic performance.