Photoacoustic imaging of head and neck cancer: Preclinical optimization and clinical translation
Rich, Laurie James
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Tumor oxygenation critically influences the response of head and neck tumors to radiation therapy (RT). Specifically, tumor hypoxia, or low tumor oxygenation, is a negative prognostic indicator of RT response in head and neck cancer. Yet, there are currently no methods used routinely in the clinic to measure tumor oxygenation. Photoacoustic imaging (PAI) is a relatively new imaging technique that exploits the optical characteristics of oxy- and deoxyhemoglobin to provide information on tissue oxygen saturation (%sO 2 ) levels. The ability of PAI to provide quantitative estimates of %sO 2 without the need for externally administered contrast agents combined with its short image acquisition times, low operating costs, lack of ionizing radiation, and relative ease of use make it ideal for clinical imaging. Although PAI is being increasingly used for mapping tumor hypoxia and cancer detection, few studies have validated PAI-based %sO 2 measurements with other radiologic techniques. The role of PAI for monitoring the response of tumors to RT has also not been systematically examined. The overall goal of this work was to validate and assess the prognostic impact of PAI-based %sO 2 measurements in head and neck cancer. In this work, I first determined the detection and sensitivity limits of our PAI system in vitro using tissue mimicking phantoms. Using optimized imaging parameters obtained in vitro, I then validated PAI-based %sO 2 measurements with two clinically relevant magnetic resonance imaging (MRI) techniques, oxygen-enhanced MRI (OE-MRI) and blood oxygenation level dependent MRI (BOLD-MRI), techniques sensitive to tissue oxygen concentration and deoxyhemoglobin levels, respectively. Studies in pre-clinical patient derived xenograft (PDX) models of head and neck squamous cell carcinoma (HNSCC) revealed that PAI was more sensitive to changes in tumor oxygenation than both BOLD- and OE-MRI. PAI was also able to detect inter- and intra-tumoral heterogeneity in %sO 2 levels and showed good spatial correlation with histology. Finally, PAI was used to monitor the response of PDX-HNSCC to RT. Increases in tumor %sO 2 following radiation were associated with significant tumor growth inhibition. Together, my observations illustrate a role in PAI for monitoring tumor oxygenation and the response of HNSCC tumors to RT.