title: Imaging of brain oxygenation with magnetic resonance imaging: A validation with positron emission tomography in the healthy and tumoural brain.
abstract: The partial pressure in oxygen remains challenging to map in the brain. Two main strategies exist to obtain surrogate measures of tissue oxygenation: the tissue saturation studied by magnetic resonance imaging (StO2-MRI) and the identification of hypoxia by a positron emission tomography (PET) biomarker with 3-[18F]fluoro-1-(2-nitro-1-imidazolyl)-2-propanol ([18F]-FMISO) as the leading radiopharmaceutical. Nonetheless, a formal validation of StO2-MRI against FMISO-PET has not been performed. The objective of our studies was to compare the two approaches in (a) the normal rat brain when the rats were submitted to hypoxemia; (b) animals implanted with four tumour types differentiated by their oxygenation. Rats were submitted to normoxic and hypoxemic conditions. For the brain tumour experiments, U87-MG, U251-MG, 9L and C6 glioma cells were orthotopically inoculated in rats. For both experiments, StO2-MRI and [18F]-FMISO PET were performed sequentially. Under hypoxemia conditions, StO2-MRI revealed a decrease in oxygen saturation in the brain. Nonetheless, [18F]-FMISO PET, pimonidazole immunohistochemistry and molecular biology were insensitive to hypoxia. Within the context of tumours, StO2-MRI was able to detect hypoxia in the hypoxic models, mimicking [18F]-FMISO PET with high sensitivity/specificity. Altogether, our data clearly support that, in brain pathologies, StO2-MRI could be a robust and specific imaging biomarker to assess hypoxia.
authors.affiliation: 1 Normandie Université, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Valable
authors.affiliation: 1 Normandie Université, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Corroyer-Dulmont
authors.affiliation: 1 Normandie Université, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen, France.
authors.forename: Ararat
authors.initials: A
authors.lastname: Chakhoyan
authors.affiliation: 1 Normandie Université, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Durand
authors.affiliation: 1 Normandie Université, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Toutain
authors.affiliation: 1 Normandie Université, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Divoux
authors.affiliation: 2 Normandie Université, UNICAEN, CEA, CNRS, ISTCT/LDM-TEP Group, Caen, France.
authors.forename: Louisa
authors.initials: L
authors.lastname: Barré
authors.affiliation: 1 Normandie Université, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen, France.
authors.forename: Eric T
authors.initials: ET
authors.lastname: MacKenzie
authors.affiliation: 1 Normandie Université, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen, France.
authors.forename: Edwige
authors.initials: E
authors.lastname: Petit
authors.affiliation: 1 Normandie Université, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Bernaudin
authors.affiliation: 1 Normandie Université, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen, France.
authors.forename: Omar
authors.initials: O
authors.lastname: Touzani
authors.affiliation: 3 Inserm, U1216, Grenoble, France.|4 Université Grenoble Alpes, Grenoble Institut des Neurosciences, Grenoble, France.
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Barbier
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002560:Cerebrovascular Circulation / Q000502:physiology; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D002534:Hypoxia, Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000097:blood*; D049268:Positron-Emission Tomography; D011916:Rats, Inbred F344; D011923:Rats, Nude; D017208:Rats, Wistar
chemical_list: D010100:Oxygen
keywords: Hypoxia; glioblastoma; magnetic resonance imaging; oxygenation; positron emission tomography; rat