Synopsis

Keywords: Tumors, Nervous system

To date, few studies have investigated the association between ADC values and tumor subtypes of adult-type diffuse gliomas based on WHO CNS5. By comparing standard, high and ultra-high b value DWI, our research found that all ADC values can differentiate IDH genotypes with ADC_8,000 having the highest AUC of 0.827, and mostly ADC values can differentiate the tumor subtypes of gliomas, with ADC_8,000 and ADC_4,000 having the highest AUC of 0.780 and 0.902, respectively. High and ultra-high b value DWI, is a potent approach in identifying IDH genotype and tumor subtype of adult-type diffuse gliomas based on WHO CNS5.

Introduction

Gliomas are primary brain tumors characterized by high morbidity and mortality¹. Isocitrate dehydrogenase (IDH) is related to the internal heterogeneity and biological behavior of glioma. Compared with IDH-wildtype gliomas, IDH-mutant gliomas have better survival, regardless of the histological grade^{2; 3}. In 2021, the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5) which places greater emphasis on genotyping was published. The adult-type diffuse gliomas are currently divided into three subtypes: (1) glioblastoma, IDH-wildtype, (2) astrocytoma, IDH-mutant, and (3) oligodendroglioma, IDH-mutant and 1p/19q-codeleted⁴. However, biopsy or localized resection may not be representative of the tumor as a whole. Recently, diffusion-weighted imaging (DWI) has been widely used for calculating a major parameter for quantifying water diffusion called the apparent diffusion coefficient (ADC) to noninvasively reflect the diffusion of water molecules in biological tissues. Moreover, high and even ultra-high b values DWI have been applied to clinical practice more frequently which gives more access to the intracellular space and membrane interactions^5-8. However, the relationship between ADC values and tumor subtypes of adult-type diffuse gliomas based on WHO CNS5 has not been discussed up to now. Therefore, the purpose of this study was to investigate the effect of ultra-high b value DWI in preoperatively identifying IDH genotype and classifying the tumor subtype of adult-type diffuse gliomas based on WHO CNS5 and to compare its diagnostic efficiency with standard and high b value DWI.

Methods

Fifty patients (26 males and 24 females) with adult-type diffuse gliomas, who underwent preoperative multi-b value DWI at 3T MR scanner (MAGNETOM Prisma, SIEMENS Healthcare, Erlangen, Germany) with a 64-channel receive-only head coil, were enrolled. A single-shot echo planer imaging sequence was used for the multiple b value DWI imaging with the following parameters: TR/TE = 3,800ms/74ms; slice thickness = 5mm, gap = 1mm; field of view (FOV) = 23cm×23cm; acquisition matrix = 128×128, reconstruction matrix = 256×256; accelerating factor with GRAPPA = 2; slice acceleration factor, 2; and pixel bandwidth = 2055Hz/pixel. The apparent diffusion coefficient (ADC) values including ADC_1,000, ADC_2,000, ADC_3,000, ADC_4,000, ADC_6,000, ADC_8,000, and ADC_10,000 in tumor parenchyma (TP) and contralateral normal-appearing white matter (NAWM) were calculated. The Mann-Whitney U test was performed to compare the differences in ADC values between tumors with different IDH genotypes as well as the ADC values across patients with glioblastoma, IDH-wildtype, astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant, and 1p/19q-codeleted. And the diagnostic performances were assessed using receiver operating characteristic (ROC) curves and the area under curve (AUC).

Results

ADC_1,000, ADC_2,000, ADC_3,000, ADC_4,000, ADC_6,000, ADC_8,000, and ADC_10,000 were significantly higher in the IDH-mutant gliomas than those in the wildtype gliomas (p < 0.05 for all), and ADC_8,000 having the highest diagnostic performance (AUC[95%CI]=0.827 [0.694; 0.919], specificity=84.62% and sensitivity=70.83%). ADC_2,000, ADC_3,000, ADC_4,000, ADC_6,000, ADC_8,000, and ADC_10,000 were significantly lower in the glioblastoma, IDH-wildtype, than those in the astrocytoma, IDH-mutant, and those in the oligodendroglioma, IDH-mutant and 1p/19q-codeleted (p < 0.05 for all), with ADC_8,000 and ADC_4,000 showing the highest diagnostic performance (AUC[95%CI]=0.780 [0.621; 0.895], specificity=81.82% and sensitivity=66.67%), (AUC[95%CI]=0.902 [0.729; 0.981], specificity=95.45% and sensitivity=83.33%). No significant difference was found for all ADC values between astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant, and 1p/19q-codeleted (p > 0.05 for all). At the same time, all ADC values were significantly lower in glioblastoma, IDH-wildtype compared with gliomas of IDH-mutant (p < 0.05 for all).

Discussion

Our research found that all ADC values were able to well differentiate IDH-mutant from IDH-wildtype gliomas. Compared with IDH-wildtype gliomas, all ADC values were significantly higher in IDH-mutant gliomas. This may be explained by the smaller tumor cells and lower tumor cell density within IDH-mutant than IDH-wildtype. We found that all ADC values, except ADC_1,000, were able to differentiate the glioblastoma, IDH-wildtype from astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant, and 1p/19q-codeleted by delineating the diffusion difference of water molecules, and those ADC values were significantly lower in glioblastoma, IDH-wildtype. The possible explanation is that glioblastoma, IDH-wildtype is a mitotically active tumor, which can restrict movement of the water molecule. In contrast, astrocytoma, and IDH-mutant are characterized by mild hypercellularity and nuclear atypia and oligodendroglioma, IDH-mutant, and 1p/19q-codelete consist of more homogeneous and looser cell composition, indicating that diffusion of the water molecule is not restricted in the tissue. By comparing the diagnostic performance of different ADC values, we found that as the b values increased, both diagnostic performance of the corresponding ADC values in identifying IDH genotype and differentiating glioblastoma, IDH-wildtype from astrocytoma, IDH-mutant seemed to increase in parallel, with the ADC values of ultra-high b values DWI having the highest diagnostic AUCs. Similarly, in differentiating glioblastoma, IDH-wildtype from oligodendroglioma, IDH-mutant, and 1p/19q-codeleted, the ADC values of high and ultra-high b values DWI showed higher diagnostic AUC. In contrast, ADC_1,000 of standard b value DWI showed poor diagnostic performance in this study. Theoretically, as the b value rises, a higher b value DWI provides better contrast with its reflection of more tissue diffusivity and less T2 shine-through effect⁹.

Conclusion

DWI is a potent approach in identifying tumor subtypes of adult-type diffuse gliomas based on WHO CNS5, with higher b value providing better diagnostic performance.

Acknowledgements

No acknowledgement found.

References

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