Application Of Multi-modal MRI Imaging Technique In Glioma Pathological Grade Prediction And Tumor Infiltration Boundary

ObjectiveIn the first part,the C6-Wistar rat model was constructed to determine whether there was tumor cell infiltration in the tumor peri-tumoral edema area.In the second part,three magnetic resonance imaging（MRI）techniques,including2D multi-voxel ¹H-MRS,3D-ASL and DKI were used in combination with quantitative analysis to analyze the the natures of tumor and the peripheral edema area of high-grade and low-grade gliomas,so as to provide more accurate imaging information for the preoperative determination of tumor grade and the surgical resection range for the neurosurgeons.Methods1.The C6-Wistar rat glioma model was constructed to determine the nature of peri-tumoral edema area.1)The construction of the C6-Wistar rat glioma model:16 male healthy Wistar rats were selected randomly,then C6 cells were injected into the caudate nucleus in the right brain of Wistar rats using the brain stereotactic instrument,and the rats were then raised normally.2)The MRI of C6-Wistar rat glioma model and pathological control:at 2-3weeks later,the postoperative Wistar rats were performed cranial MRI,DTI and single-voxel 2D ¹H-MRS examinations.After completing the examinations,the brain tissues of rats were dissected,prepared into paraffin block,sliced according to the MRI images,stained with HE and the pathological sections were observed under the optical microscope.2.The preliminary study on the application of DKI,MRS and 3D-ASL techniques in predicting the pathological grade of glioma patients and the the nature of the peri-tumoral edema area:53 glioma patients confirmed at the Pathology Department of our hospital were collected and performed cranial MRI,DKI,3D-ASL and 2D ¹H-MRS examinations before surgery.Then,the patients were divided into low-grade glioma group and high-grade glioma group;whereas the lesions were classified as tumor parenchymal enhancement area,proximal peri-tumoral edema area,moderate peri-tumoral edema area,distal peri-tumoral edema area,and normal contralateral white matter area.Then,the maximum edema cross sections of lesions were selected,respectively,to quantitatively measure the values of fraction of kurtosis anisotropy（FK）,mean diffusion kurtosis（MK）,axial kurtosis（AK）,radial kurtosis（RK）,apparent diffusion coefficient（ADC）,cerebral blood flow（CBF）,relative cerebral blood flow（r BCF）,CHO/Cr and NAA/C material metabolism ratios.3.The one-way analysis of variance（ANOVA）was adopted for inter-group comparisons of means among multiple samples.For intra-group comparison,LSD and SNK methods were applied in the case of homogeneity of variance,whereas the Wilcoxon rank sum test was used in the case of heterogeneity of variance between two groups,and Kruskal-Wallis rank sum test was utilized among multiple groups.The Spearman rank correlation analysis was used for correlation analysis,and a difference of P<0.05 indicated statistical significance.Then,the receiver operating characteristic（ROC）curve was plotted for the significantly different indexes to calculate their sensitivity,specificity,area under the curve（AUC）and diagnostic threshold.Results1.Research results on the construction of the C6-Wistar glioma rat model and tumor infiltration boundary:1)6 cases showed the peri-tumoral edema zones,and cystic necrotic regions were observed in the lesions of 4 cases.Upon enhanced scanning,11 cases had moderate-strong enhancement of tumor parenchyma,and the enhancement range was smaller than the lesion range shown on T2WI images.On MRS images,11lesions showed elevated CHO/Cr value whereas decreased NAA/Cr value.On DTI images,11 lesions exhibited declined FA value and elevated ADC value.2)In terms of pathology,the tumors in all the 11 rats were high-grade gliomas,as observed under the microscope,which showed obvious nuclear atypia.In some tumor tissues,small vascular proliferation was seen,there was a clear boundary between the tumor parenchyma and the edema zone,while the edema zone was ill-defined from the normal brain tissue,and scattered tumor cells were observed within the edema zone.2.Preliminary research results on the application of DKI,¹H-MRS and 3D-ASL techniques in predicting the pathological grade of glioma patients and the peri-tumoral infiltration boundary:1)The values of MK,AK,RK,r CBF and CHO/Cr in the tumor parenchyma of high-grade glioma group were greatly lower than those in low-grade glioma group,and the differences were statistically significant（P<0.05）.The ADC value in the tumor parenchyma of high-grade glioma group was lower than that in low-grade glioma group,and the difference was of statistical significance（P<0.01）.The correlation coefficients of MK,AK,RK,r CBF,CHO/Cr and ADC with pathological grade were 0.605,0.569,0.591,0.359,0.298 and-0.513,respectively（P<0.05）.2)The MK value（AUC,0.873;95%CI,0.781-0.965;P<0.01;sensitivity,81.8%;specificity,83.9%）had the highest diagnostic efficacy for high-grade glioma,with the threshold of 0.728.In addition,the ADC value（AUC,0.811;95%CI,0.698-0.924;P<0.01;sensitivity,58.1%;specificity,95.5%）had a certain diagnostic value for low-grade glioma,with the threshold of 892.285×10^-3 mm²/s.3)In high-grade glioma,differences in MK,AK,RK,ADC,r CBF,CHO/Cr and NAA/Cr between the tumor parenchyma and proximal peri-tumoral edema area were statistically significant（P<0.05）.Difference in CHO/Cr value between the proximal peri-tumoral edema area and moderate peri-tumoral edema area was of statistical significance（P<0.01）,and difference in NAA/Cr value between the proximal peri-tumoral edema area and distal peri-tumoral edema area was statistically significant（P<0.05）.In low-grade glioma,the NAA/Cr and CHO/Cr values between tumor parenchyma and proximal peri-tumoral edema area showed statistically significant differences（P<0.01）,and difference in the NAA/Cr value between the proximal peri-tumoral edema area and distal peri-tumoral edema area was statistically significant（P<0.05）.Differences in various indexes of each peri-tumoral edema area between high-grade and low-grade gliomas were not significant（P>0.05）.4)MK,AK and CHO/Cr values showed high accuracy in classifying the high-grade glioma parenchyma（AUC,0.905,0.944 and 0.982）.The RK and r CBF values exhibited certain accuracy in classifying high-grade glioma parenchyma（AUC,0.838 and 0.793）.The ADC value had certain accuracy in classifying the proximal peri-tumoral edema area of high-grade glioma（AUC,0.788）.The CHO/Cr value showed certain accuracy in classifying the low-grade glioma parenchyma（AUC,0.779）.5)Difference in FK value was not significant between high-grade and low-grade glioma parenchyma and diverse edema areas.6)The lesions were divided into well-defined group and ill-defined group according to the tumor enhancement boundary on T1WI images.As a result,no significant difference was observed in the AK,RK,MK,FK,r CBF,CHO/Cr and NAA/Cr values in tumor parenchyma and proximal peri-tumoral edema area between two groups（P>0.05）.Differences in AK value in moderate and distal peri-tumoral edema areas between two groups were significant（P<0.05）.Conclusion1.The pathology of experimental animal model confirms that,there is a clear boundary between the glioma parenchyma and the edema zone,while the edema zone is ill-defined from the normal brain tissues,and scattered tumor cells can be observed within the edema zone.The DTI and MRS parameters（FA,ADC,CHO/Cr and NAA/Cr）can be used to distinguish tumor from the normal peripheral brain parenchyma,and the FA value can effectively evaluate the infiltration degree of glioma cells.2.The MK and ADC values have the highest diagnostic efficacy in predicting the glioma grade:MK>0.728 reveals a high probability of high-grade glioma,while ADC>892.285×10^-3 mm²/s suggests a great probability of low-grade glioma.3.The CHO/Cr value can be used as a non-invasive yet effective supplementary means to evaluate the glioma infiltration boundary.4.For tumor with no enhancement upon T1WI enhanced scanning,the 1H-MRS technique can provide effective imaging information regarding the surgical resection range.5.The surgical range should be designed to maximally resect the tumor parenchyma and the region within 1 cm away from the tumor enhanced edge,in the premise of guaranteeing the brain functional region.