Magnetic resonance imaging to detect tumor hypoxia in brain malignant disease: A systematic review of validation studies

Tumor hypoxia indicates a worse prognosis in brain malignancies; however, current gold-standard methods for assessing tumor hypoxia are invasive and often inaccessible. Magnetic Resonance Imaging (MRI) is widely available, but its validity for identifying tumor hypoxia or hypoxia-related neoangiogenesis is not well characterized. A systematic literature search was performed across PubMed and Embase Databases. The search query identified MRI studies that validated hypoxia-surrogate imaging sequences against gold-standard hypoxia or neoangiogenesis detection methods in patients with brain malignancies. Literature screen identified 23 manuscripts published between 2007 and 2022. Among conventional MRI sequences, peritumoral edema and signal change after contrast administration were associated with gold-standard oxygen-assessment methods. T2*- and T2′-derived measures were associated with gold-standard methods, while reports on quantitative measures of oxygen extraction fraction were conflicting. Fiber density, tissue cellularity, blood volume, vascular transit time, and permeability measurements were associated with gold-standard methods, whereas blood flow measurements yielded conflicting results. MRI measures are promising surrogates for tumor hypoxia or hypoxia-related neoangiogenesis. Additional studies are needed to reconcile disparate findings. Future sensitivity analyses are needed to establish the MRI methods most accurate at identifying tumor hypoxia.