Noninvasive Optoacoustic Imaging of Oxygen Saturation Reveals Hypoxic Hematopoietic Bone Marrow during Systemic Inflammation

Inflammation drives various diseases, including cardiovascular, neurodegenerative, and oncological disorders, by altering immune cell dynamics in hematopoietic niches. The bone marrow is the primary site for hematopoietic stem and progenitor cell activity. Here, we present a novel, noninvasive approach using multispectral optoacoustic tomography (MSOT) to track oxygenation dynamics in the murine calvarial bone marrow during acute systemic inflammation induced by lipopolysaccharide (LPS). Our MSOT system provided real-time, label-free imaging of hemoglobin oxygen saturation (sO2), revealing significant reductions in sO2 levels in lipopolysaccharide-treated mice, indicative of increased oxygen consumption. Co-registration with microCT enabled precise vascular mapping. Hypoxia was confirmed by ex vivo Pimonidazole staining and optical imaging and was associated with elevated neutrophil counts and enhanced hematopoietic activation. These findings demonstrate MSOT's potential for noninvasive imaging of marrow oxygenation, offering insights into inflammation-driven hematopoietic activation and supporting the development of therapies targeting oxygen-sensitive pathways.