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Updated: Nov 4, 2025
Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma
Published on: September 13, 2022
Hypermetabolism and impaired cerebrovascular reactivity beyond the standard MRI-identified tumor border indicate
Martina Sebök1,2, Christiaan Hendrik Bas van Niftrik1,2, Giovanni Muscas1,3
1Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Background:
Diffuse gliomas exhibit diffuse infiltrative growth, often beyond the magnetic resonance imaging (MRI)-detectable tumor lesion. Within this lesion, hypermetabolism and impaired cerebrovascular reactivity (CVR) are found, but its exact distribution pattern into the peritumoral environment is unknown. Our aim was to better characterize the extent of diffuse glioma tissue infiltration, beyond the visible lesion (ie, beyond the T1-contrast-enhancing lesion and/or T2/FLAIR-defined tumor border), with metabolic positron emission tomography (PET), and functional MRI CVR (blood oxygenation-level-dependent CVR [BOLD-CVR]) mapping.
Methods:
From a prospective glioma database, 18 subjects (19 datasets) with diffuse glioma (n = 2 with anaplastic astrocytoma, n = 10 with anaplastic oligodendroglioma, and n = 7 with glioblastoma) underwent a BOLD-CVR and metabolic PET study between February 2016 and September 2019, 7 of them at primary diagnosis and 12 at tumor recurrence. In addition, 19 matched healthy controls underwent an identical BOLD-CVR study. The tumor lesion was defined using high-resolution anatomical MRI. Volumes of interest starting from the tumor lesion outward up to 30 mm were created for a detailed peritumoral PET and BOLD-CVR tissue analysis. Student's t test was used for statistical analysis.
Results:
Patients with diffuse glioma exhibit impaired BOLD-CVR 12 mm beyond the tumor lesion (P = .02) with normalization of BOLD-CVR values after 24 mm. Metabolic PET shows a difference between the affected and contralateral hemisphere of 6 mm (P = .05) with PET values normalization after 12 mm.
Conclusion:
We demonstrate hypermetabolism and impaired CVR beyond the standard MRI-defined tumor border, suggesting active tumor infiltration in the peritumoral environment.
