In vivophotoacoustic lifetime imaging of tumor hypoxia in small animals

Abstract

Abstract. Tumor hypoxia is an important factor in assessment of both cancer progression and cancer treatment efficacy. This has driven a substantial effort toward development of imaging modalities that can directly measure oxygen distribution and therefore hypoxia in tissue. Although several approaches to measure hypoxia exist, direct measurement of tissue oxygen through an imaging approach is still an unmet need. To address this, we present a new approach based on in vivo application of photoacoustic lifetime imaging (PALI) to map the distribution of oxygen partial pressure (pO 2 ) in tissue. This method utilizes methylene blue, a dye widely used in clinical applications, as an oxygen-sensitive imaging agent. PALI measurement of oxygen relies upon pO 2 -dependent excitation lifetime of the dye. A multimodal imaging system was designed and built to achieve ultrasound (US), photoacoustic, and PALI imaging within the same system. Nude mice bearing LNCaP xenograft hindlimb tumors were used as the target tissue. Hypoxic regions were identified within the tumor in a combined US/PALI image. Finally, the statistical distributions of pO 2 in tumor, normal, and control tissues were compared with measurements by a needle-mounted oxygen probe. A statistically significant drop in mean pO 2 was consistently detected by both methods in tumors. © 2013 Society of Photo-Optical Instrumentation Engineers (SPIE)

Intermittent Hypoxia-induced Changes in Tumor-associated Macrophages and Tumor Malignancy in a Mouse Model of Sleep Apnea

“…The presence of hypoxia is a common feature of human solid tumors, even if hypoxic regions are not homogenously distributed across the tumor and are usually confined to the core, where blood supply is less abundant (26). The content and location of TAMs within the tumor is positively correlated with the degree of overall hypoxia in liver metastases from breast and colorectal tumors (27).…”

The Clinical Importance of Assessing Tumor Hypoxia: Relationship of Tumor Hypoxia to Prognosis and Therapeutic Opportunities

“…Photoacoustic lifetime imaging (PALI) measures the lifetime of an oxygensensitive dye, which is proportional to local oxygen concentration. This technique has been recently used to detect hypoxia in tumors and correlated against pO 2 electrode measurements measurements (249). After a local tumor injection of methylene blue in xenograft mice bearing LNCaP (prostate cancer) tumors, electrode pO 2 measurements and PALI imaging data detected lower oxygen concentrations in the tumor tissue (20 mmHg), confirming the presence of tumor hypoxia.…”

Photoacoustic Imaging of Vascular Hemodynamics: Validation with Blood Oxygenation Level–Dependent MR Imaging

“…As a result, there has been widespread interest in the use of PAI in medical applications, particularly in cancer research. PAI increasingly is being used to map tumor hypoxia and monitor changes in tumor perfusion and oxygenation after treatment (4,5). However, despite widespread interest in its clinical translation, very few studies have validated PAI results with standard radiologic techniques (6,7).…”