Simultaneous Molecular and Hypoxia Imaging of Brain Tumors <i>In Vivo</i> Using Spectroscopic Photoacoustic Tomography

TLDR

Noninvasive molecular and functional imaging in vivo holds promise for detecting and monitoring diverse physiological conditions in animals and humans. The authors introduce spectroscopic photoacoustic tomography (SPAT) as a novel noninvasive modality combining strong optical absorption contrast with high ultrasonic spatial resolution. SPAT exploits optical contrast to spectroscopically separate signals from oxyhemoglobin, deoxyhemoglobin, and a molecular contrast agent, enabling simultaneous molecular and functional imaging. In nude mouse brains bearing human U87 glioblastomas, SPAT achieved high‑resolution imaging of an integrin‑targeted contrast agent and of hemoglobin oxygen saturation, revealing tumor neovascular hypoxia and suggesting a link between hemodynamics and tumor biomarkers.

Abstract

Noninvasive molecular and functional imaging in vivo is promising for detecting and monitoring various physiological conditions in animals and ultimately humans. To this end, we present a novel noninvasive technology, spectroscopic photoacoustic tomography (SPAT), which offers both strong optical absorption contrast and high ultrasonic spatial resolution. Optical contrast allows spectroscopic separation of signal contributions from multiple optical absorbers (e.g., oxyhemoglobin, deoxyhemoglobin, and a molecular contrast agent), thus enabling simultaneous molecular and functional imaging. SPAT successfully imaged with high resolution the distribution of a molecular contrast agent targeting integrin overexpressed in human U87 glioblastomas in nude mouse brains. Simultaneously, SPAT also imaged the hemoglobin oxygen saturation and the total hemoglobin concentration of the vasculature, which revealed hypoxia in tumor neovasculature. Therefore, SPAT can potentially lead to better understanding of the interrelationships between hemodynamics and specific biomarkers associated with tumor progression.