title: In vivo optical imaging of tumor and microvascular response to ionizing radiation.
abstract: 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.
authors.affiliation: Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Azusa
authors.initials: A
authors.lastname: Maeda
authors.forename: Michael K K
authors.initials: MK
authors.lastname: Leung
authors.forename: Leigh
authors.initials: L
authors.lastname: Conroy
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Chen
authors.forename: Jiachuan
authors.initials: J
authors.lastname: Bu
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Lindsay
authors.forename: Shani
authors.initials: S
authors.lastname: Mintzberg
authors.forename: Carl
authors.initials: C
authors.lastname: Virtanen
authors.forename: Julissa
authors.initials: J
authors.lastname: Tsao
authors.forename: Neil A
authors.initials: NA
authors.lastname: Winegarden
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Wang
authors.forename: Lily
authors.initials: L
authors.lastname: Morikawa
authors.forename: I Alex
authors.initials: IA
authors.lastname: Vitkin
authors.forename: David A
authors.initials: DA
authors.lastname: Jaffray
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hill
authors.forename: Ralph S
authors.initials: RS
authors.lastname: DaCosta
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D055806:Microvessels / Q000378:metabolism / Q000503:physiopathology / Q000528:radiation effects*; D009389:Neovascularization, Pathologic; D061848:Optical Imaging / Q000295:instrumentation / Q000379:methods*; D011853:Radiobiology / Q000295:instrumentation / Q000379:methods*; D013927:Thrombosis / Q000150:complications; D013997:Time Factors; D041623:Tomography, Optical Coherence; D059467:Transcriptome / Q000528:radiation effects; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000150:complications / Q000235:genetics / Q000473:pathology; D014965:X-Rays