Oxygen enhanced MRI accurately identifies, quantifies, and maps hypoxia in preclinical cancer models.
AuthorsO'Connor, James P B
AffiliationInstitute of Cancer Sciences, University of Manchester
MetadataShow full item record
AbstractThere is a clinical need for non-invasive biomarkers of tumor hypoxia for prognostic and predictive studies, radiotherapy planning and therapy monitoring. Oxygen enhanced MRI (OE-MRI) is an emerging imaging technique for quantifying the spatial distribution and extent of tumor oxygen delivery in vivo. In OE-MRI, the longitudinal relaxation rate of protons (∆R1) changes in proportion to the concentration of molecular oxygen dissolved in plasma or interstitial tissue fluid. Therefore, well-oxygenated tissues show positive ∆R1. We hypothesized that the fraction of tumor tissue refractory to oxygen challenge (lack of positive ∆R1, termed "Oxy-R fraction") would be a robust biomarker of hypoxia in models with varying vascular and hypoxic features. Here we demonstrate that OE-MRI signals are accurate, precise and sensitive to changes in tumor pO2 in highly vascular 786-0 renal cancer xenografts. Furthermore, we show that Oxy-R fraction can quantify the hypoxic fraction in multiple models with differing hypoxic and vascular phenotypes, when used in combination with measurements of tumor perfusion. Finally, Oxy-R fraction can detect dynamic changes in hypoxia induced by the vasomodulator agent hydralazine. In contrast, more conventional biomarkers of hypoxia (derived from blood oxygenation-level dependent MRI and dynamic contrast-enhanced MRI) did not relate to tumor hypoxia consistently. Our results show that the Oxy-R fraction accurately quantifies tumor hypoxia non-invasively and is immediately translatable to the clinic.
CitationOxygen enhanced MRI accurately identifies, quantifies, and maps hypoxia in preclinical cancer models. 2015: Cancer Res
- Mapping Hypoxia in Renal Carcinoma with Oxygen-enhanced MRI: Comparison with Intrinsic Susceptibility MRI and Pathology.
- Authors: Little RA, Jamin Y, Boult JKR, Naish JH, Watson Y, Cheung S, Holliday KF, Lu H, McHugh DJ, Irlam J, West CML, Betts GN, Ashton G, Reynolds AR, Maddineni S, Clarke NW, Parker GJM, Waterton JC, Robinson SP, O'Connor JPB
- Issue date: 2018 Sep
- Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non-small Cell Lung Cancer.
- Authors: Salem A, Little RA, Latif A, Featherstone AK, Babur M, Peset I, Cheung S, Watson Y, Tessyman V, Mistry H, Ashton G, Behan C, Matthews JC, Asselin MC, Bristow RG, Jackson A, Parker GJM, Faivre-Finn C, Williams KJ, O'Connor JPB
- Issue date: 2019 Jul 1
- Noninvasive tumor hypoxia measurement using magnetic resonance imaging in murine U87 glioma xenografts and in patients with glioblastoma.
- Authors: Linnik IV, Scott ML, Holliday KF, Woodhouse N, Waterton JC, O'Connor JP, Barjat H, Liess C, Ulloa J, Young H, Dive C, Hodgkinson CL, Ward T, Roberts D, Mills SJ, Thompson G, Buonaccorsi GA, Cheung S, Jackson A, Naish JH, Parker GJ
- Issue date: 2014 May
- Fast and sensitive dynamic oxygen-enhanced MRI with a cycling gas challenge and independent component analysis.
- Authors: Moosvi F, Baker JHE, Yung A, Kozlowski P, Minchinton AI, Reinsberg SA
- Issue date: 2019 Apr
- Preliminary study of oxygen-enhanced longitudinal relaxation in MRI: a potential novel biomarker of oxygenation changes in solid tumors.
- Authors: O'Connor JP, Naish JH, Parker GJ, Waterton JC, Watson Y, Jayson GC, Buonaccorsi GA, Cheung S, Buckley DL, McGrath DM, West CM, Davidson SE, Roberts C, Mills SJ, Mitchell CL, Hope L, Ton NC, Jackson A
- Issue date: 2009 Nov 15