Assessment of blood oxygen saturation using spectroscopic photoacoustic imaging as a biomarker for disease progression in a small-animal leukemia model

Acute lymphoblastic leukemia (ALL) interacts with bone marrow cells, creating hypoxic niches that stabilize HIF-1α and promote chemotherapeutic resistance. Spectrosocopic photoacoustic (PA) imaging is a label-free, noninvasive technique that probes the in vivo oxygenation status of hemoglobin, resulting in a measurement of oxygen saturation (SO₂) and providing a surrogate measure of tissue hypoxia. This work investigates multispectral PA imaging to assess the SO₂ in the femoral bone marrow in mice. Preliminary work was performed to assess the capability of imaging through bone, followed by an oxygen challenge to determine the magnitude of systemic SO₂ changes measurable in wild type mice. Furthermore, a pilot study to compare SO₂ measured in a murine model of ALL versus in healthy controls was performed to investigate a correlation between SO₂ changes in the femoral bone marrow and disease progression. Study results show that femoral SO₂ can be measured with a variation less than 10% in wild type mice over multiple time-points. In the oxygen challenge, a 10% difference in systemic SO₂ was observed between 100% and 21% O₂ inhalation conditions. Additionally, leukemic mice demonstrate significantly more variation in femoral SO₂ over the length of the femur than control mice at day 14 post-inoculation, indicating that femoral SO₂ is affected by leukemic disease progression. This work demonstrates the feasibility of observing changes in leukemic disease progression through the measurement of SO₂ with spectroscopic PA imaging, which could help develop a more complete understanding of the interplay of the local microenvironment with leukemogenesis.