https://phaidra.vetmeduni.ac.at/o:3075 Non-Contrast-Enhanced Multiparametric MRI of the Hypoxic Tumor Microenvironment Allows Molecular Subtyping of Breast Cancer: A Pilot Study Bartsch, Silvester J. Silvester J. Bartsch Medical University of Vienna Pinker, Katja Katja Pinker 0000-0002-2722-7331 Memorial Sloan Kettering Cancer Center Helbich, Thomas H. Thomas H. Helbich 0000-0003-3169-778X Medical University of Vienna Laimer-Gruber, Daniela Daniela Laimer-Gruber Medical University of Vienna Kenner, Lukas Lukas Kenner 0000-0003-2184-1338 University of Veterinary Medicine Vienna / Medical University of Vienna Fürböck, Christoph Christoph Fürböck Medical University of Vienna Friske, Joachim Joachim Friske Medical University of Vienna Brožová, Klára Klára Brožová 0000-0002-0050-9478 University of Veterinary Medicine Vienna / Medical University of Vienna Ehret, Viktoria Viktoria Ehret 0000-0003-1487-8693 Medical University of Vienna MDPI text eng 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. Angiogenesis; Hallmarks; Diffusion; Expression; Pericytes; Receptor; Benign; Hif-1 http://creativecommons.org/licenses/by/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:3075/download 10.3390/cancers16020375 https://phaidra.vetmeduni.ac.at/o:605 application/pdf Cancers 16(2) (2024) Cancers 16 2 692.71 kB 2024