Physiological MRI Biomarkers in the Differentiation Between Glioblastomas and Solitary Brain Metastases

Purpose!#!Glioblastomas (GB) and solitary brain metastases (BM) are the most common brain tumors in adults. GB and BM may appear similar in conventional magnetic resonance imaging (cMRI). Their management strategies, however, are quite different with significant consequences on clinical outcome. The aim of this study was to evaluate the usefulness of a previously presented physiological MRI approach scoping to obtain quantitative information about microvascular architecture and perfusion, neovascularization activity, and oxygen metabolism to differentiate GB from BM.!##!Procedures!#!Thirty-three consecutive patients with newly diagnosed, untreated, and histopathologically confirmed GB or BM were preoperatively examined with our physiological MRI approach as part of the cMRI protocol.!##!Results!#!Physiological MRI biomarker maps revealed several significant differences in the pathophysiology of GB and BM: Central necrosis was more hypoxic in GB than in BM (30 %; P = 0.036), which was associated with higher neovascularization activity (65 %; P = 0.043) and metabolic rate of oxygen (48 %; P = 0.004) in the adjacent contrast-enhancing viable tumor parts of GB. In peritumoral edema, GB infiltration caused neovascularization activity (93 %; P = 0.018) and higher microvascular perfusion (30 %; P = 0.022) associated with higher tissue oxygen tension (33 %; P = 0.020) and lower oxygen extraction from vasculature (32 %; P = 0.040).!##!Conclusion!#!Our physiological MRI approach, which requires only 7 min of extra data acquisition time, might be helpful to noninvasively distinguish GB and BM based on pathophysiological differences. However, further studies including more patients are required

Metabolic Tumor Microenvironment Characterization of Contrast Enhancing Brain Tumors Using Physiologic MRI

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