Hypoxia-correlated functional photoacoustic tomography enhances breast tumor detection

Breast photoacoustic tomography (PAT) enables noninvasive vascular imaging with high spatial resolution and optical contrast, but most prior studies have focused on static anatomy rather than functional dynamics. We introduce hypoxia-correlation functional PAT (hc-PAT), which leverages the abnormal vascular reactivity of malignant tumors. Participants underwent alternating breath-holding and normal breathing to induce transient systemic hypoxia, monitored by pulse oximetry. Simultaneous hc-PAT imaging was performed, and voxel-wise correlation with the oxygenation waveform generated functional maps. Malignant tumors showed significantly higher correlation coefficients than surrounding tissue, clearly delineating lesions consistent with magnetic resonance imaging (MRI) and tumor pathophysiology. Quantitative analysis revealed greater inter-breast asymmetry in malignant versus benign cases ( $p\sim 0.014$ ). hc-PAT also sensitively tracked response to neoadjuvant chemotherapy, showing reduced hypoxia reactivity alongside MRI-confirmed tumor shrinkage. This pilot study demonstrates that hc-PAT can enhance breast cancer detection using endogenous functional contrast, suggesting the potential for sensitive, injection-free functional imaging that warrants validation in larger cohorts.