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Updated: Mar 6, 2026
Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
Published on: July 31, 2017
Recurrence of glioblastoma is associated with elevated microvascular transit time heterogeneity and increased hypoxia
Andreas Stadlbauer1,2, Kim Mouridsen3, Arnd Doerfler4
11 Department of Neurosurgery, University of Erlangen-Nürnberg, Erlangen, Germany.
Abstract:
Dynamic susceptibility contrast (DSC) perfusion MRI provide information about differences in macro- and microvasculature when executed with gradient-echo (GE; sensitive to macrovasculature) and spin-echo (SE; sensitive to microvasculature) contrast. This study investigated whether there are differences between macro- and microvascular transit time heterogeneity (MVTH and µVTH) and tissue oxygen tension (PO2mit) in newly-diagnosed and recurrent glioblastoma. Fifty-seven patients with glioblastoma (25 newly-diagnosed/32 recurrent) were examined with GE- and SE-DSC perfusion sequences, and a quantitative blood-oxygen-level-dependent (qBOLD) approach. Maps of MVTH, µVTH and coefficient of variation (MCOV and µCOV) were calculated from GE- and SE-DSC data, respectively, using an extended flow-diffusion equation. PO2mit maps were calculated from qBOLD data. Newly-diagnosed and recurrent glioblastoma showed significantly lower ( P ≤ 0.001) µCOV values compared to both normal brain and macrovasculature (MCOV) of the lesions. Recurrent glioblastoma had significantly higher µVTH ( P = 0.014) and µCOV ( P = 0.039) as well as significantly lower PO2mit values ( P = 0.008) compared to newly-diagnosed glioblastoma. The macrovasculature, however, showed no significant differences. Our findings provide evidence of microvascular adaption in the disorganized tumor vasculature for retaining the metabolic demands in stress response of therapeutically-uncontrolled glioblastomas. Thus, µVTH and PO2mit mapping gives insight into the tumor microenvironment (vascular and hypoxic niches) responsible for therapy resistance.
Insights
Recurrent glioblastoma shows altered microvasculature and lower oxygen levels compared to newly-diagnosed tumors. These microvascular changes (µVTH) and tissue oxygen tension (PO2mit) offer insights into therapy resistance.
Area of Science:
- Neuroimaging
- Oncology
- Medical Physics
Background:
- Dynamic susceptibility contrast (DSC) perfusion MRI, using gradient-echo (GE) and spin-echo (SE) sequences, differentiates macro- and microvasculature.
- Glioblastoma (GBM) presents distinct macro- and microvascular characteristics between newly-diagnosed and recurrent stages.
- Understanding these vascular differences is crucial for assessing tumor aggressiveness and therapeutic resistance.
Purpose of the Study:
- To investigate differences in macro- and microvascular transit time heterogeneity (MVTH and µVTH) and tissue oxygen tension (PO2mit) between newly-diagnosed and recurrent glioblastoma.
- To correlate these vascular parameters with tumor stage and potential therapy resistance mechanisms.
Main Methods:
- Fifty-seven glioblastoma patients (25 newly-diagnosed, 32 recurrent) underwent GE- and SE-DSC perfusion MRI and quantitative blood-oxygen-level-dependent (qBOLD).
- Maps of MVTH, µVTH, MCOV, and µCOV were derived from DSC data using an extended flow-diffusion model.
- PO2mit maps were calculated from qBOLD data.
Main Results:
- Both newly-diagnosed and recurrent GBM exhibited significantly lower microvascular coefficient of variation (µCOV) than normal brain or lesion macrovasculature (MCOV).
- Recurrent GBM demonstrated significantly higher microvascular transit time heterogeneity (µVTH) and µCOV, alongside significantly lower tissue oxygen tension (PO2mit) compared to newly-diagnosed GBM.
- No significant differences were observed in the macrovasculature between the two groups.
Conclusions:
- Microvascular adaptations occur in disorganized GBM vasculature to meet metabolic demands under stress, particularly in therapeutically resistant recurrent tumors.
- µVTH and PO2mit mapping provide valuable insights into the tumor microenvironment, identifying vascular and hypoxic niches associated with therapy resistance in glioblastoma.
