Breast tumor hypoxia mapping using ultrasound guided diffuse optical tomography

Abstract

Tumor hypoxia is an important indicator of tumor metabolism and tumor response to various forms of therapy. Currently, no imaging modality exists that can directly map tumor hypoxia non-invasively. We present an ultrasound guided diffuse optical imaging technique for precisely measuring the tumor oxygenation. The approach employs ultrasound structural information as a-prior knowledge for diffuse optical imaging. Hypoxia mapping is achieved using endogenous chromophores such as oxy- and deoxy- hemoglobin in the tissue. Because oxy- and deoxy- hemoglobin respond differently at different wavelengths, four different laser diodes of wavelengths 740 nm, 780 nm, 808 nm and 830 nm were used for mapping tumor hypoxia by diffuse optical imaging. Hypoxia model experiments were performed using phantoms at different oxygenation conditions (Hemoglobin oxygen saturation: 14%-92%) representing the hemoglobin oxygenation range in tissue. Targets of different sizes mimicking different development stages of breast tumors, 1.0 cm to 2.5 cm diameter in 0.5 cm steps, were tested to validate the oxygen saturation measurement accuracy with target size. The absolute deviations between the estimated hemoglobin oxygen saturations from absorption maps and oxygen measurements obtained using a pO₂ electrode were less than 8% over the measured range of oxygen saturations (14% - 92%). An inhomogeneous cocentric blood phantom of deoxygenated center core and oxygenated outer shell was imaged and deoxy- and oxy- hemoglobin maps revealed corresponding distributions which correlate with inhomogeneous deoxy- and oxy- distributions frequently seen in advanced breast cancers located in the depth range of 1-3 cm.