Metabolic Tumor Microenvironment Characterization of Contrast Enhancing Brain Tumors Using Physiologic MRI.
Andreas StadlbauerFranz MarholdStefan OberndorferGertraud HeinzMax ZimmermannMichael BuchfelderElisabeth HeynoldThomas M M KinfePublished in: Metabolites (2021)
The tumor microenvironment is a critical regulator of cancer development and progression as well as treatment response and resistance in brain neoplasms. The available techniques for investigation, however, are not well suited for noninvasive in vivo characterization in humans. A total of 120 patients (59 females; 61 males) with newly diagnosed contrast-enhancing brain tumors (64 glioblastoma, 20 brain metastases, 15 primary central nervous system (CNS) lymphomas (PCNSLs), and 21 meningiomas) were examined with a previously established physiological MRI protocol including quantitative blood-oxygen-level-dependent imaging and vascular architecture mapping. Six MRI biomarker maps for oxygen metabolism and neovascularization were fused for classification of five different tumor microenvironments: glycolysis, oxidative phosphorylation (OxPhos), hypoxia with/without neovascularization, and necrosis. Glioblastoma showed the highest metabolic heterogeneity followed by brain metastasis with a glycolysis-to-OxPhos ratio of approximately 2:1 in both tumor entities. In addition, glioblastoma revealed a significant higher percentage of hypoxia (24%) compared to all three other brain tumor entities: brain metastasis (7%; p < 0.001), PCNSL (8%; p = 0.001), and meningioma (8%; p = 0.003). A more aggressive biological brain tumor behavior was associated with a higher percentage of hypoxia and necrosis and a lower percentage of remaining vital tumor tissue and aerobic glycolysis. The proportion of oxidative phosphorylation, however, was rather similar (17-26%) for all four brain tumor entities. Tumor microenvironment (TME) mapping provides insights into neurobiological differences of contrast-enhancing brain tumors and deserves further clinical cancer research attention. Although there is a long roadmap ahead, TME mapping may become useful in order to develop new diagnostic and therapeutic approaches.
Keyphrases
- contrast enhanced
- high resolution
- newly diagnosed
- magnetic resonance imaging
- magnetic resonance
- resting state
- white matter
- brain metastases
- papillary thyroid
- endothelial cells
- end stage renal disease
- ejection fraction
- functional connectivity
- high density
- computed tomography
- single cell
- squamous cell
- randomized controlled trial
- diabetic retinopathy
- machine learning
- vascular endothelial growth factor
- blood brain barrier
- prognostic factors
- cerebral ischemia
- mass spectrometry
- peritoneal dialysis
- childhood cancer
- deep learning
- squamous cell carcinoma
- high intensity
- young adults
- patient reported outcomes
- cerebrospinal fluid
- optical coherence tomography