phaidra.vetmeduni.ac.at o:3075 DOI 10.3390/cancers16020375 Non-Contrast-Enhanced Multiparametric MRI of the Hypoxic Tumor Microenvironment Allows Molecular Subtyping of Breast Cancer: A Pilot Study Tumor neoangiogenesis is an important hallmark of cancer progression, triggered by alternating selective pressures from the hypoxic tumor microenvironment. Non-invasive, non-contrast-enhanced multiparametric MRI combining blood-oxygen-level-dependent (BOLD) MRI, which depicts blood oxygen saturation, and intravoxel-incoherent-motion (IVIM) MRI, which captures intravascular and extravascular diffusion, can provide insights into tumor oxygenation and neovascularization simultaneously. Our objective was to identify imaging markers that can predict hypoxia-induced angiogenesis and to validate our findings using multiplexed immunohistochemical analyses. We present an in vivo study involving 36 female athymic nude mice inoculated with luminal A, Her2+, and triple-negative breast cancer cells. We used a high-field 9.4-tesla MRI system for imaging and subsequently analyzed the tumors using multiplex immunohistochemistry for CD-31, PDGFR-β, and Hif1-α. We found that the hyperoxic-BOLD-MRI-derived parameter ΔR2* discriminated luminal A from Her2+ and triple-negative breast cancers, while the IVIM-derived parameter fIVIM discriminated luminal A and Her2+ from triple-negative breast cancers. A comprehensive analysis using principal-component analysis of both multiparametric MRI- and mpIHC-derived data highlighted the differences between triple-negative and luminal A breast cancers. We conclude that multiparametric MRI combining hyperoxic BOLD MRI and IVIM MRI, without the need for contrast agents, offers promising non-invasive markers for evaluating hypoxia-induced angiogenesis. eng Angiogenesis; Hallmarks; Diffusion; Expression; Pericytes; Receptor; Benign; Hif-1 2024-06-06T09:38:18.810Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Bartsch;Silvester J.; FN:Silvester J. Bartsch END:VCARD BEGIN:VCARD VERSION:3.0 N:Pinker;Katja; FN:Katja Pinker X-ORCID:https://orcid.org/0000-0002-2722-7331 END:VCARD BEGIN:VCARD VERSION:3.0 N:Helbich;Thomas H.; FN:Thomas H. Helbich X-ORCID:https://orcid.org/0000-0003-3169-778X END:VCARD BEGIN:VCARD VERSION:3.0 N:Laimer-Gruber;Daniela; FN:Daniela Laimer-Gruber END:VCARD BEGIN:VCARD VERSION:3.0 N:Kenner;Lukas; FN:Lukas Kenner X-ORCID:https://orcid.org/0000-0003-2184-1338 END:VCARD BEGIN:VCARD VERSION:3.0 N:Fürböck;Christoph; FN:Christoph Fürböck END:VCARD BEGIN:VCARD VERSION:3.0 N:Friske;Joachim; FN:Joachim Friske END:VCARD BEGIN:VCARD VERSION:3.0 N:Brožová;Klára; FN:Klára Brožová X-ORCID:https://orcid.org/0000-0002-0050-9478 END:VCARD BEGIN:VCARD VERSION:3.0 N:Ehret;Viktoria; FN:Viktoria Ehret X-ORCID:https://orcid.org/0000-0003-1487-8693 END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 709340 https://phaidra.vetmeduni.ac.at/o:3075 https://phaidra.vetmeduni.ac.at/api/object/o:3075/thumbnail LOMv1.0 discipline