gms | German Medical Science

Objective: Microvascular proliferation is a diagnostic marker and an independent prognostic parameter for glioblastomas. A biological link between hypoxia and angiogenesis is generally accepted. In this study, we introduce a multiparametric magnetic resonance imaging (MRI) approach that enables the combined examination of oxygen metabolism and angiogenesis in gliomas.

Method: Thirty-five patients with low-grade or recurrent high gliomas (6 WHO°II, 10 WHO°III, 19 glioblastomas) were examined using vascular architecture mapping (VAM) and multiparametric quantitative BOLD (mp-qBOLD). For VAM a dual contrast agent injections approach was used to obtain GE- and SE-EPI DSC perfusion MRI data. For mp-qBOLD, additional T2*- and T2-mapping sequences were performed. Custom-made in-house MatLab software was used for VAM and mp-qBOLD data postprocessing to obtain maps of the vascular architecture MRI biomarkers microvessel radius (RU), density (NU), and type indicator (MTI) as well as maps of the oxygen metabolism MRI biomarkers oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO₂).

Results: Low-grade glioma (LGGs) showed increased OEF compared to contralateral normal-appearing brain (CNB; p=0.027), peritumoral (predominant edematous) regions (p=0.028), and high-grade gliomas (HGGs, WHO°III and IV, p<0.001). No tumor-induced angiogenic activity within LGGs and their peritumoral regions, but in fact a lower microvessel density NU compared to cNB/peritumoral (p=0.046) and HGGS (p=0.011 and p<0.001) were detected. HGGs (WHO°III and IV) demonstrated significantly decreased OEF and increased NU values compared to cNB (p=0.005 and p<0.001). Glioblastomas showed large areas with significantly increased CMRO₂ (p<0.001). Areas with highest CMRO₂ values were positively correlated with high NU. Maps of MTI allowed differentiation between supplying arterial (small areas with warm colors) and draining venous microvasculature (widespread areas, especially in glioblastoma with cool colors). These findings can be interpreted as excessive oxygen demand of HGGs, which is covered and even oversupplied by microvascular changes, induced by angiogenesis.

Conclusions: Combined assessment of tumor oxygen metabolism and angiogenesis provide insight into tumor biology and thus may be beneficial for grading and therapy monitoring of gliomas. However, investigations in more well-defined patient populations and histological validations are necessary.