Establishing a small animal imaging facility Design considerations and operation Julie L Sutcliffe Ph.D. Assistant Professor Director, Cyclotron and Radiochemistry Facility The Center for Molecular and Genomic Imaging Department of Department of Biomedical Engineering Biomedical Engineering
Is a dedicated small animal imaging facility necessary? � Increasing number of dedicated small animal imaging systems e.g. microPET, microCAT, microSPECT etc � Increasing number of mouse models of human disease � Increasingly sophisticated and specific multi modal molecular probes � Multimodality imaging facilities that can house animals, support the instrumentation and provide investigators with tools, methods and infrastructure to perform SUCCESSFUL imaging studies is important. Department of Biomedical Engineering
Acknowledgements/ Disclaimer � Timothy C. Doyle , D.Phil, Scientific Director, Stanford Small Animal Imaging Facility, timbo@pmgm2.stanford.edu � Chris Flask , Case Center for Imaging Research flask@uhrad.com � Jason Lewis , Assistant Professor, Wash U, LewisJas@mir.wustl.edu � Martin G. Pomper , M.D., Ph.D., Johns Hopkins Medical Institutions mpomper@jhmi.edu � Steve Rendig , Manager, Center for Molecular and Genomic Imaging, UCDavis � David Stout, Ph.D ., Director, Crump Small Animal Imaging Facility, UCLA Crump Institute for Molecular Imaging DStout@mednet.ucla.edu � Gregory R. Wojtkiewicz , Massachusetts General Hospital / Harvard University gwojtkiewicz@PARTNERS.ORG � Pat Zanzonico , PhD, Memorial Sloan-Kettering Cancer Center, zanzonip@mskcc.org Department of Biomedical Engineering
Funding opportunities � Why these people They are 8 of the 12 nationally funded centre from SAIR grants � What is a SAIR grant? Small Animal Imaging Resource Program (U24) (RFA) Number: RFA-CA-07-004 http://grants1.nih.gov/grants/guide/rfa-files/RFA-CA-07-004.html The SAIR Program (SAIRP) was established in 1999 with the funding of five sites. These grants support: (a) shared imaging resources to be used by cancer investigators (b) research related to small animal imaging technology or methodology (c) training of both professional and technical support personnel interested in the science and techniques of small animal imaging. Department of Biomedical Engineering
Funding opportunities “Small Animal Imaging Resources (SAIRs) will enhance capabilities for conducting basic, translational, and clinical cancer research relevant to the mission of the NCI. Major goals of this initiative are to increase efficiency, synergy, and innovation of such research and to foster research interactions that cross disciplines, approaches, and levels of analysis. Building and strengthening such links holds great potential for better understanding cancer, and ultimately, for better treatment and prevention.” � The total amount to be awarded is $18 million over 5 years. � The NCI anticipates awarding eight small animal imaging resource grants in FY 2007. � Current recipients include Memorial Sloan-Kettering Cancer Center, Johns Hopkins University, Massachusetts General Hospital/Harvard University, Duke University, Stanford University, University of Michigan, University of Arizona, University of Pennsylvania, Washington University, Case Western Reserve University, UCLA and UCDavis. Department of Biomedical Engineering
Modalities? � Is your centre a dedicated small animal facility? 8 of 8 � What imaging modalities do you use? microPET 8 of 8 microCT 8 of 8 SPECT/CT 6 of 8 Optical 8 of 8 Ultrasound 5 of 8 MRI 5 of 8 Department of Biomedical Engineering
Modalities continued? � What current instrumentation do you have? microPET : microPET R4, microPET P4, microPET Focus 120,microPET-Focus 220 MicroPET II microCAT : Imtek MicroCAT II SPECT/CT : GammaMedica Optical : Xenogen IVIS 100 Ultrasound: Somoline Antares, Acuson Sequoia, VisualSonics MRI : Bruker, Varian, Magnex � What is the most widely used modality? 4 of 7 said optical imaging Department of Biomedical Engineering
Facility design � What is the square footage of your facility? This ranged from 1850-6500 Use what you have Flow is critical in small floor plans � How long did your facility take to become operational? 1-2 years to become operational 3- 5years in the design and build � Do you have a vivarium adjacent to the imaging facility 8 of 8 have adjacent barrier facilities with holding areas for hot animals Department of Biomedical Engineering
How busy are you ? � How many current users do you have 20-200 academic users 1- 5 industrial users � How many scans are performed/ week A scan is a single image 30-350 Majority of scans being microPET or optical Department of Biomedical Engineering
Probe development � Do you have a probe development group? 8 of 8 said yes � Do you have a dedicated cyclotron 8 of 8 have at least 1 dedicated cyclotron � What are the most frequently used probes FDG, FLT, FIAU, Fmiso, FHBG, 64 Cu- ATSM and 64 Cu- antibodies Department of Biomedical Engineering
What do you do in terms of infection control? � Handling animals in biosafety cabinets � Spraying with antibacterial cleaner before and after each study � Use isolation chambers microPET-CT Optical Imaging Isolation Chamber Isolation Chamber Allows for reproducible positioning, constant gas anesthesia, multi-modality imaging capability (PET, CT, MR), barrier for immunocompromised mice and rats and temperature control. The optical chamber provides gas anesthesia and barrier conditions. Heating is provided externally. Department of Biomedical Engineering
Animal Health Issues � Multi-user, multi-species facility � Potential for spread of infectious disease � Needs thought regarding What animals come into the facility? How are they are handled within the facility? How are surfaces in the facility cleaned? Where and how are animals kept for longitudinal studies? Department of Biomedical Engineering
Why Worry? � Infectious contamination can wipe out breeding colonies � Etiologies fall into 5 categories: – Those that the animal lives with as normal flora. Do not cause any clinical problems and not known to have direct affect on research. Example: Normal gut flora. – Those that the animal becomes infected by without clinical signs or evidence of disease, but can have impact on research. Example: Mouse parvovirus. – Those that the animal becomes infected by that are opportunistic, normally don’t cause clinical signs but based on research or immune status can cause clinical signs and disease and directly affect research Example: Pneumocystis sp.. – Those that the animal becomes infected by that can cause clinical signs and have direct affects on research Example: Mouse Hepatitis Virus – Those that the animal becomes infected by without clinical signs or evidence of disease, but can have impact on specific types of research and are difficult to manage or prevent spread. Example: Pinworms. Department of Biomedical Engineering
Common Mouse Pathogens � Mouse Parvoviruses (MPV) � MPV leads to persistent infections, especially in lymph nodes � Transmission: fecal and urinary shed � Stable in environment for months � Mouse Hepatitis Virus � Respiratory and enteric symptoms � Transmission fecal-oral, aerosol, direct contact � Most frequent and contagious pathogen in mice � Murine Pinworms � Common, difficult to get rid of, easily transmitted Department of Biomedical Engineering
Animal monitoring and intervention � What physiological monitoring do you perform? Temperature, respiration rate, ECG � What sampling do you perform during a study Blood sampling via cardiac puncture post sacrifice, tail nick, retro-orbital venous plexus, arterial lines, carotid/femoral arteries � How do you inject contrast agent? Directly into tail vein, catheter, warm the tail, awake and asleep Department of Biomedical Engineering
Staffing � How many staff do you have in your facility 2-20 Manager, computer scientists, lab techs, animal techs, Director, Research associates On average 6 people � How do you advertise your facility Website, retreats, free pilot studies, lectures � What sort of training to you have for users Animal handling, anesthesia, scanner operation (mainly for optical only) Most centers provide a full service for PET studies. Department of Biomedical Engineering
Lessons learnt � Actual usage is always considerably less than projected � Full cost recovery through charges is virtually impossible to achieve � Plan for success, make sure the architecture as scope to expand � External investigators expect everything to be turn key � Proper handling of animals to obtain meaningful and reproducible data � People….hire good ones � Cleanliness Department of Biomedical Engineering
Specific Design and Operation considerations at UCDavis � Facility objectives � Site planning � Radiation Safety � Infection Control � Animal Housing � Data Management System � Recharge � Staffing Department of Biomedical Engineering
microPET � The microPET(r) R4 (12 cm bore) � The microPET(r) P4 (22 cm bore) � The microPET(r) Focus 120 (12 cm bore) � The microPET(r) Focus 220 (22 cm bore size) � Inveon PET (12 cm bore). The site planning for all is about the same with power, AC and exhaust for anesthesia gas. Department of Biomedical Engineering
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