The Application Of Multimodal MRI In The Evaluation Of Pathological Grading,genotype And Prognosis Of Human Glioma

BackgroundGlioma is one of the most common primary malignant tumor in human brain and is mainly treated by neurosurgery.However,different pathological grading of gliomas might influence the therapy responses and prognosis.Some researchers have reported the relationship of the imaging characteristics of MRI with pathological grading and cell proliferation of gliomas,but there are still lack of systemic investigation of multimodal MRI with clinical characteristic of gliomas.Multimodal MRI is a combination of conventional MRI and advanced MRI technologies.In this study,we explore the relationship between the imaging features and pathological grading,cell proliferation,gene phenotypes and prognosis of gliomas in order to find some potential imging markers which can reflect pathological grading,cell proliferation,gene phenotypes and prognosis of gliomas noninvasively.ObjectiveIn this study,multimodal MRI technology,that is combination of conventional MRI and advanced MRI including DWI,DTI,DTT as well as 1H-MRS will be applied.By analysis of imaging characteristic of conventional MRI and quantitative characteristics of functional MRI(r ADC value of DWI,r FA value of DTI,Cho/Cr,Cho/NAA,NAA/Cr ratio of MRS),we will calculate the correlations of multimodal MRI with pathological grading,cell proliferation,gene phenotypes and prognosis of gliomas in order to find some potential imging markers which can reflect pathological grading,cell proliferation,gene phenotypes and prognosis of gliomas noninvasively.Method(1)Total of 76 gliomas patients was recruited between Oct 2014 to Dec 2017,including 61 males and 15 females,with mean age of 51.29 years old,ranging from 19 to 79 years old.Informed consents were obtained from all patients.(2)All patients received conventional MRI and advanced MRI scan.Tumor location,size,enhancement features and circumstance of tumor body(necrosis,bleeding,cystic change and peritumoral edema)were recorded.Furthermore,r ADC value of DWI and r FA value of DTI in the center of primary tumor and contralateral white matters was recorded.Meanwhile,the ratio of Cho/Cr,Cho/NAA,and NAA/Cr was also recorded.We investigated diffusion tensortractography(DTT)between the fiber bundles in primary tumor regions and in contralateral white matters by continuous tracing method.There are three basic types: displacement,infiltration and interrupt.(3)The expression of Ki-67 was tested by immunohistochemistry S-P staining.MGMT promoter methylation was tested by pyrosequencing.IDH1/2 gene mutations was tested by PCR combined sequencing.The integration of 1p19 q was tested by fluorescence in situ hybridization.Finally,we did a follow-up study for all the patients with time period of 1 to 36 months.(4)SPSS version 21.0 is used for data analysis and P<0.05 is considered to be significant.Results(1)In conventional MRI scan,there are significant differences of enhancement,peritumoral edema and necrosis between LGG and HGG groups.Higher rate of enhancement phenomenon,peritumoral edema and necrosis are found in HGG group.(2)There are significant correlations of peritumoral edema,necrosis and enhancement with Ki-67 expressions.The higher grade of peritumoral edema,enhancement and necrosis indicated high positive rate of Ki-67.(3)DTT suggest that the completeness of white matter has correlation with tumor grade and Ki-67 index.DTT damage is much often found in HGG and Ki-67 expression is usually up-regulated.(4)r FA value was lower in HGG than in LGG.r FA is negatively correlated with Ki-67 expression(P=0.016)and positively correlated with Cho/Cr ratio(P=0.018).(5)In genetic analysis,significant differences are found among IDH1 gene mutation,MGMT gene promoter methylation and 1p19 q co-deletion in different tumor grade(LGG and HGG).Among them,IDH1 gene mutation,MGMT gene promoter methylation and 1p19 q co-deletion had a higher rate in LGG group than in HGG group.There are significant differences among the status of IDH1 gene mutation,MGMT gene promoter methylation and 1p19 q co-deletion in peritumoral edema.The peritmoral edema also indicates unmethlated MGMT,wild IDH1 and tact 1p19 q in glioma.(6)Higher r FA value and r ADC value are found in glioma with 1p19 q co-deletion.Higher NAA/Cr ratio could also be found in MGMT gene promoter methylation.(7)In survival analysis,the OS rate in LGG is higher in LGG than HGG(Log-rank P=0.011).(8)In conventional MRI scan,peritumoral edema has correlation with survival rate(Log-rank P<0.001).In advanced MRI scan,Cho/Cr ratio is correlated with survival rate(Log-rank P=0.029)Conclusion(1)Peritumoral edema,necrosis and enhancement in conventional MRI scan could not only distinguish tumor grade,but also reflect cell proliferation of gliomas.The peritmoral edema could indicate unmethlated MGMT,wild IDH1 and tact 1p19 q in glioma.(2)The status of DTT,r FA value of DTI and NAA/Cr and Cho/Cr ratio in 1H-MRS test have significant correlation with tumor grade and cell proliferation.The combination of r FA value of DTI and r ADC of DWI could distinguish the integration of 1p19 q.NAA/Cr ratio in 1H-MRS test could distinguish MGMT promoter methylation.(3)Peritumoral edema demonstrated by conventional MRI scan and Cho/Cr ratio in 1H-MRS test have correlation with glioma prognosis,and which could be a potential marker for prognosis of gliomas patients.