Hypoxia Detection in Infiltrative Astrocytoma: Ferumoxytol-based Quantitative BOLD MRI with Intraoperative and Histologic Validation.

Abstract

Purpose To validate ferumoxytol-based quantitative blood oxygenation level-dependent (BOLD) MRI for mapping oxygenation of human infiltrative astrocytomas by using intraoperative measurement of tissue oxygen tension and histologic staining. Materials and Methods Fifteen patients with infiltrative astrocytomas were recruited into this prospective multicenter study between July 2014 and December 2016. Prior to treatment, participants underwent preoperative quantitative BOLD MRI with ferumoxytol to generate tissue oxygen saturation (StO₂) maps. Two intratumoral sites were identified, one with low StO₂ and one with high StO₂. Neuronavigation was used to locate sites intraoperatively for insertion of oxygen-sensing probes to measure local tissue oxygen tension (PtO₂). Biopsies from both sites were taken and stained for markers of hypoxia (hypoxia-inducible factor 1α, carbonic anhydrase IX) and neoangiogenesis (vascular endothelial growth factor, endoglin [CD105]). Spearman correlation and nonparametric sign-rank tests were used to analyze data. Results Ten patients with median age of 58.5 years (interquartile range, 25 years; four men and six women) completed the study. Because there is no linear relationship between StO₂ and PtO₂, the ratios of low to high StO₂ versus low to high PtO₂ in each patient were compared and a significant correlation was found (r = 0.73; P = .01). Pathologic analyses revealed differences between carbonic anhydrase IX (P = .03) for sites of low StO₂ versus high StO₂. CD105 displayed a similar trend but was not significant (P = .09). Conclusion Ferumoxytol-based quantitative blood oxygenation level-dependent MRI can potentially be used as a noninvasive surrogate for oxygenation mapping in infiltrative astrocytomas. This technique can potentially be integrated in treatment planning for aggressive targeting of hypoxic areas in tumors.