Comparison of Genetic Profiles and Prognosis of High-Grade Gliomas Using Quantitative and Qualitative MRI Features: A Focus on G3 Gliomas

Abstract

Objective To evaluate the association of MRI features with the major genomic profiles and prognosis of World Health Organization grade III (G3) gliomas compared with those of glioblastomas (GBMs). Materials and Methods We enrolled 76 G3 glioma and 155 GBM patients with pathologically confirmed disease who had pretreatment brain MRI and major genetic information of tumors. Qualitative and quantitative imaging features, including volumetrics and histogram parameters, such as normalized cerebral blood volume (nCBV), cerebral blood flow (nCBF), and apparent diffusion coefficient (nADC) were evaluated. The G3 gliomas were divided into three groups for the analysis: with this isocitrate dehydrogenase ( IDH )-mutation, IDH mutation and a chromosome arm 1p/19q -codeleted (IDHmut1p/19qdel), IDH mutation, 1p/19q -nondeleted (IDHmut1p/19qnondel), and IDH wildtype (IDHwt). A prediction model for the genetic profiles of G3 gliomas was developed and validated on a separate cohort. Both the quantitative and qualitative imaging parameters and progression-free survival (PFS) of G3 gliomas were compared and survival analysis was performed. Moreover, the imaging parameters and PFS between IDHwt G3 gliomas and GBMs were compared. Results IDHmut G3 gliomas showed a larger volume ( p = 0.017), lower nCBF ( p = 0.048), and higher nADC ( p = 0.007) than IDHwt. Between the IDHmut tumors, IDHmut1p/19qdel G3 gliomas had higher nCBV ( p = 0.024) and lower nADC ( p = 0.002) than IDHmut1p/19qnondel G3 gliomas. Moreover, IDHmut1p/19qdel tumors had the best prognosis and IDHwt tumors had the worst prognosis among G3 gliomas ( p < 0.001). PFS was significantly associated with the 95th percentile values of nCBV and nCBF in G3 gliomas. There was no significant difference in neither PFS nor imaging features between IDHwt G3 gliomas and IDHwt GBMs. Conclusion We found significant differences in MRI features, including volumetrics, CBV, and ADC, in G3 gliomas, according to IDH mutation and 1p/19q codeletion status, which can be utilized for the prediction of genomic profiles and the prognosis of G3 glioma patients. The MRI signatures and prognosis of IDHwt G3 gliomas tend to follow those of IDHwt GBMs.

Hemodynamic Imaging in Cerebral Diffuse Glioma—Part B: Molecular Correlates, Treatment Effect Monitoring, Prognosis, and Future Directions

“…Examples of efforts in this direction include the availability of the Cancer Genome Atlas imaging datasets through the Cancer Imaging Archive ( Last accessed on 21 December 2021). More importantly, this hypothesis has been also extensively explored in hemodynamic imaging [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. In this section, we focus in particular on hemodynamic correlates of isocitrate dehydrogenase (IDH) mutation status, 1p19q codeletion, O 6 -methylguanine-DNA methyl-transferase (MGMT) promoter methylation, and epidermal growth factor receptor (EGFR) alterations.…”

“…The IDHmut and the accumulation of the “oncometabolite” 2-HG are associated with the hypermethylation phenotype, called glioma CpG island methylator, ultimately altering metabolism to promote malignant growth [ 36 , 37 ]. As the prognostic implications of reliable pre-operative identification of this molecular marker could significantly alter the clinical management decisions including the radicality of the surgical resection, several studies have investigated the potential for IDH status prediction in diffuse gliomas using hemodynamic imaging [ 10 , 11 , 20 , 29 , 30 , 32 , 38 ]. Consistently with “traditional” tumor grading, IDHmut gliomas tend to exhibit decreased perfusion and permeability with respect of their wild-type counterpart.…”

“…Consistently with “traditional” tumor grading, IDHmut gliomas tend to exhibit decreased perfusion and permeability with respect of their wild-type counterpart. Lower DSC-cerebral blood volume(CBV) [ 10 , 20 , 29 , 32 , 39 , 40 ], as with lower DSC-cerebral blood flow (CBF) [ 30 , 38 ], were found to be able to discriminate IDHmut versus IDHwt. Percentage of signal recovery (PSR) was also reported to be lower in IDHwt tumors [ 40 ].…”

“…Oligodendroglioma is genetically defined as a tumor harboring a IDH1/IDH2 mutation involving the co-deletion of chromosome arms 1p and 19q. Diagnosis can be obtained only using pathological tissue after a biopsy or resection [ 3 , 47 ] but hemodynamic imaging has also shown potential for the identification of IDH 1p/19q codeletion status as part of the differentiation of oligodendroglioma from the IDH mutant 1p/19q non-deleted astrocytomas and IDHwt glioblastomas [ 10 , 11 , 12 , 30 , 48 ]. The pre-operative identification of 1p/19q is clinically relevant as oligodendrogliomas are characterized by a lower impact of the extent of resection with respect of IDHmut astrocytoma, whereas they also display a better response to cytotoxic agents and increased OS [ 49 ].…”

“…The pre-operative identification of 1p/19q is clinically relevant as oligodendrogliomas are characterized by a lower impact of the extent of resection with respect of IDHmut astrocytoma, whereas they also display a better response to cytotoxic agents and increased OS [ 49 ]. DSC-CBV has been found to be increased in IDHmut 1p/19q codel grade 3 gliomas as opposed to IDHmut 1p/19q nodel grade 3, [ 30 , 48 , 50 , 51 ] suggesting denser and more heterogenous vascular distribution in the former [ 48 ], but decreased with respect to IDHwt glioblastomas [ 10 , 50 , 52 ]. In a meta-analysis by Delgado and Delgado investigating whether DSC can differentiate between grade 2 and 3 gliomas, diagnostic accuracy was substantially decreased for differentiating between oligodendroglioma grades 2 and 3 [ 53 ].…”