In vivo optical imaging of tumor and microvascular response to ionizing radiation

• Published in: PloS one 2012-08, Vol.7 (8), p.e42133-e42133
• Main Authors: Maeda, Azusa, Leung, Michael K K, Conroy, Leigh, Chen, Yonghong, Bu, Jiachuan, Lindsay, Patricia E, Mintzberg, Shani, Virtanen, Carl, Tsao, Julissa, Winegarden, Neil A, Wang, Yanchun, Morikawa, Lily, Vitkin, I Alex, Jaffray, David A, Hill, Richard P, DaCosta, Ralph S
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Bioinformatics; Biology; Biophysics; Cancer; Cancer cells; Cancer therapies; Care and treatment; Cell Line, Tumor; Diagnosis; Drug dosages; Female; Health care networks; Hospitals; Humans; Imaging; Imaging techniques; Ionizing radiation; Mammography; Medical imaging; Medical research; Medicine; Mice; Microscopy; Microvasculature; Microvessels - metabolism; Microvessels - physiopathology; Microvessels - radiation effects; Neovascularization, Pathologic; Oncology; Optical Imaging - instrumentation; Optical Imaging - methods; Optical microscopy; Radiation; Radiation therapy; Radiobiology - instrumentation; Radiobiology - methods; Radiotherapy; Solid tumors; Studies; Thrombosis - complications; Time Factors; Tissues; Tomography; Tomography, Optical Coherence; Transcriptome - radiation effects; Tumor cells; Tumors; Uterine Cervical Neoplasms - blood supply; Uterine Cervical Neoplasms - complications; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; X-Rays
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0042133

Radiotherapy is a widely used cancer treatment. However, understanding how ionizing radiation affects tumor cells and their vasculature, particularly at cellular, subcellular, genetic, and protein levels, has been limited by an inability to visualize the response of these interdependent components within solid tumors over time and in vivo. Here we describe a new preclinical experimental platform combining intravital multimodal optical microscopy for cellular-level longitudinal imaging, a small animal x-ray microirradiator for reproducible spatially-localized millimeter-scale irradiations, and laser-capture microdissection of ex vivo tissues for transcriptomic profiling. Using this platform, we have developed new methods that exploit the power of optically-enabled microscopic imaging techniques to reveal the important role of the tumor microvasculature in radiation response of tumors. Furthermore, we demonstrate the potential of this preclinical platform to study quantitatively--with cellular and sub-cellular details--the spatio-temporal dynamics of the biological response of solid tumors to ionizing radiation in vivo.