University of Veterinary Medicine Vienna 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. https://phaidra.vetmeduni.ac.at/o:3075 en TEXT article Angiogenesis; Hallmarks; Diffusion; Expression; Pericytes; Receptor; Benign; Hif-1 2024 2024 Bartsch, Silvester J. (Medical University of Vienna) Pinker, Katja (Memorial Sloan Kettering Cancer Center) Helbich, Thomas H. (Medical University of Vienna) Laimer-Gruber, Daniela (Medical University of Vienna) Kenner, Lukas (University of Veterinary Medicine Vienna / Medical University of Vienna) Fürböck, Christoph (Medical University of Vienna) Friske, Joachim (Medical University of Vienna) Brožová, Klára (University of Veterinary Medicine Vienna / Medical University of Vienna) Ehret, Viktoria (Medical University of Vienna) MDPI