Project Summary/Abstract: Irradiation, Preclinical Imaging, and Microscopy The Irradiation, Preclinical Imaging, and Microscopy Shared Resource (IPIM) provides a comprehensive array of sophisticated cancer relevant diagnostic imaging and therapeutic instrumentation/techniques for cells, tissues, and large and small animals, with a focus on preclinical work that sets the stage for subsequent rapid clinical translation. Irradiation services are provided with a 137Cs irradiator for use on cells and animals. Optical cellular imaging and electron microscopy provides multiple types of confocal, TIRF and wide-field fluorescence microscopy imaging, as well as scanning and transmission electron microscopy. Rodent imaging components include PET, CT, MRI, Bioluminescence/Fluorescent (Xenogen/IVIS), and VisualSonics Vevo 770 high- frequency ultrasound. Large animal imaging includes MRI, fMRI, CT, PET, ultrasound, fluoroscopy/ angiography, and intra-operative MRI/CT as part of the unique Center for Surgical Innovation (CSI). Since its opening during the current funding period, CSI has enabled a total of 7 peer-reviewed research grants, 5 of which are from NCI. Notable CSI projects include development, imaging, and treatment of a human-porcine xenograft brain tumor model, development of MRI-compatible instrumentation for facilitation of head and neck cancer surgeries performed in the MRI-intraoperative environment, and development of a novel intraoperative nerve imaging agent. The capabilities of the CSI are currently available in only a few of the largest clinical research institutions, and IPIM is distinct in having similar capabilities for use in large animal studies. Since 2015, IPIM facilities have been utilized by 55 NCCC Members from all 4 NCCC Research Programs (CPS [2], CBT [22], ICI [16], TEC [15]). NCCC Funded Member Users represented 72% of Total Users, and we request only 20% of Total IPIM budget from CCSG funding. Examples of NCCC Member-supported projects include dual modality/dual agent imaging (Davis, Pogue and Samkoe [TEC]), fundamental mechanisms associated with membrane traffic control microvascular permeability, angiogenesis and inflammation that drive tumor vasculature and subsequent treatment (Stan, Turk, Fiering, Noelle [ICI] and Pogue [TEC]); and Cherenkov irradiation as a real-time dosimetry tool in the radiation oncology setting (Pogue, Gladstone, Hoopes, and Jarvis [TEC]). In addition to providing outstanding viable imaging, IPIM will focus on accurately combining / co- registering the extensive array of radiological imaging techniques with live cell imaging, molecular targeting and genetics that will lead the way into the next generation of diagnosis and therapy. The resource is staffed by highly qualified research directors and experienced resource managers that maintain instrumentation, provide technical support, educate NCCC researchers, and are instrumental in upgrading IPIM technologies. Recent enhancements have included upgrading of the NCCC small animal 9.4T MRI. Pending improvements include replacement of our small animal CT and whole animal IVIS fluorescent/bioluminescent imagers and a dedicated effort to co-register anatomic imaging parameters with molecular histopathology and genetics.