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Research ArticleBrain Tumor Imaging

Advanced Distance-Resolved Evaluation of the Perienhancing Tumor Areas with FLAIR Hyperintensity Indicates Different ADC Profiles by MGMT Promoter Methylation Status in Glioblastoma

Gergely Bertalan, Nicolin Hainc, Fabian Dominik Von Dehn, Tibor Hortobágyi, Andrea Bink, Emilie Le Rhun, Michael Weller and Zsolt Kulcsar
American Journal of Neuroradiology February 2025, 46 (2) 302-310; DOI: https://doi.org/10.3174/ajnr.A8493
Gergely Bertalan
aFrom the Department of Neuroradiology (G.B., N.H., F.D.v.D., A.B., Z.K.), University Hospital Zürich, Zürich, Switzerland
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Nicolin Hainc
aFrom the Department of Neuroradiology (G.B., N.H., F.D.v.D., A.B., Z.K.), University Hospital Zürich, Zürich, Switzerland
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  • ORCID record for Nicolin Hainc
Fabian Dominik Von Dehn
aFrom the Department of Neuroradiology (G.B., N.H., F.D.v.D., A.B., Z.K.), University Hospital Zürich, Zürich, Switzerland
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Tibor Hortobágyi
bInstitute of Neuropathology (T.H.), University Hospital Zürich, Zürich, Switzerland
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  • ORCID record for Tibor Hortobágyi
Andrea Bink
aFrom the Department of Neuroradiology (G.B., N.H., F.D.v.D., A.B., Z.K.), University Hospital Zürich, Zürich, Switzerland
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Emilie Le Rhun
cDepartment of Neurology (E.L.R., M.W.), University Hospital Zürich, Zürich, Switzerland
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Michael Weller
cDepartment of Neurology (E.L.R., M.W.), University Hospital Zürich, Zürich, Switzerland
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Zsolt Kulcsar
aFrom the Department of Neuroradiology (G.B., N.H., F.D.v.D., A.B., Z.K.), University Hospital Zürich, Zürich, Switzerland
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Abstract

BACKGROUND AND PURPOSE: Whether differences in the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status of glioblastoma (GBM) are reflected in MRI markers remains largely unknown. In this work, we analyze the ADC in the perienhancing infiltration zone of GBM according to the corresponding MGMT status by using a novel distance-resolved 3D evaluation.

MATERIALS AND METHODS: One hundred one patients with IDH wild-type GBM were retrospectively analyzed. GBM was segmented in 3D with deep learning. Tissue with FLAIR hyperintensity around the contrast-enhanced tumor was divided into concentric distance-resolved subvolumes. Mean ADC was calculated for the 3D tumor core and for the distance-resolved volumes around the core. Differences in group mean ADC between patients with MGMT promoter methylated (mMGMT, n = 43) and MGMT promoter unmethylated (uMGMT, n = 58) GBM was analyzed with Wilcoxon signed rank test.

RESULTS: For both mMGMT and uMGMT GBM, mean ADC values around the tumor core significantly increased as a function of distance from the core toward the periphery of the perienhancing FLAIR hyperintensity (approximately 10% increase within 5 voxels with P < 001). While group mean ADC in the tumor core was not significantly different, the distance-resolved ADC profile around the core was approximately 10% higher in mMGMT than in uMGMT GBM (P < 10−8 at 5 voxel distance from the tumor core).

CONCLUSIONS: Distance-resolved volumetric ADC analysis around the tumor core reveals tissue signatures of GBM imperceptible to the human eye on conventional MRI. The different ADC profiles around the core suggest epigenetically influenced differences in perienhancing tissue characteristics between mMGMT and uMGMT GBM.

ABBREVIATIONS:

AUC
area under the curve
GBM
glioblastoma
IDH
Isocitrate dehydrogenase
MGMT
O6-methylguanine-DNA methyltransferase
mMGMT
MGMT methylated glioblastoma
PE
perienhancing FLAIR hyperintensity
PIZ
perienhancing infiltration zone
ROC
receiver operating characteristic
SD
standard deviation
T1c
postcontrast T1-weighted image
TC
T1 contrast-enhanced tumor
TCtotal
tumor core including contrast-enhanced tumor and corresponding necrotic part
uMGMT
MGMT unmethylated glioblastoma
  • © 2025 by American Journal of Neuroradiology
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American Journal of Neuroradiology: 46 (2)
American Journal of Neuroradiology
Vol. 46, Issue 2
1 Feb 2025
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Cite this article
Gergely Bertalan, Nicolin Hainc, Fabian Dominik Von Dehn, Tibor Hortobágyi, Andrea Bink, Emilie Le Rhun, Michael Weller, Zsolt Kulcsar
Advanced Distance-Resolved Evaluation of the Perienhancing Tumor Areas with FLAIR Hyperintensity Indicates Different ADC Profiles by MGMT Promoter Methylation Status in Glioblastoma
American Journal of Neuroradiology Feb 2025, 46 (2) 302-310; DOI: 10.3174/ajnr.A8493

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FLAIR Hyperintensity and MGMT in Glioblastoma
Gergely Bertalan, Nicolin Hainc, Fabian Dominik Von Dehn, Tibor Hortobágyi, Andrea Bink, Emilie Le Rhun, Michael Weller, Zsolt Kulcsar
American Journal of Neuroradiology Feb 2025, 46 (2) 302-310; DOI: 10.3174/ajnr.A8493
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