Background

Small Animal Imaging Resource Program (SAIRP) grants support shared imaging research resources to be used by cancer investigators and support research related to small animal imaging technology. SAIRs will enhance capabilities for conducting basic, clinical, and translational cancer research relevant to the mission of the NCI. Major goals of these resources 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.

Small animal models, particularly genetically engineered mice, are increasingly recognized as powerful discovery tools in cancer research. The potential that could be realized by the use of animal models has not yet fully been realized. One of the limitations is the need to sacrifice the animals to perform tissue or molecular analysis. This prevents researchers from observing in vivo the natural or perturbed evolution of the processes under study. Functional, molecular, and morphologic quantitative imaging techniques are an important tool for providing data about biochemical, genetic or pharmacological processes in vivo, and repetitively in the same animal. The SAIRP program is envisioned as enhancing such multidisciplinary activities by supporting coordinated shared research resources for NIH-funded investigators performing cancer research. SAIRs offer a unique opportunity for multidisciplinary teams within the cancer research community to address critical cancer research questions.

Objectives and Scope

Small Animal Imaging Resource Programs (SAIRs) provide:

• Multiple imaging technologies for small animals, emphasizing, but not limited to, those technologies which can provide biochemical, genetic or pharmacological information in vivo.
• Technology research and development on innovative new imaging technologies appropriate for small animals, as well as refinement and development of technologies already established.
• Capabilities and personnel to assist in the development and/or production of necessary probes for the imaging technologies provided.
• Capabilities and personnel to aid in small animal anesthesia and care, as well as to consult on the optimal use of animals in connection with the imaging experiments.

Resources

The SAIR will use approximately one half to two thirds of its resources and time to provide imaging services and collaboration to cancer-related research projects.

Current SAIRP Institutions and Principal Investigators ¹

University of Michigan ²
Brian Ross, Ph.D.
bdross@umich.edu ³

MD Anderson Cancer Center ⁴
John Hazle, Ph.D. and Juri Gelovani, M.D., Ph.D.
jhazle@mdanderson.org ⁵

University of Pennsylvania ⁶
Jerry Glickson, Ph.D.
glickson@mail.med.upenn.edu ⁷

Memorial Sloan-Kettering Cancer Center ⁸
Jason Koutcher, Ph.D.
koutchej@mskcc.org ⁹

Washington University ¹⁰
Joseph Ackerman, Ph.D.
ackerman@wuchem.wustl.edu ¹¹

Duke University ¹²
G. Allan Johnson, Ph.D.
gaj@orion.mc.duke.edu ¹³

Johns Hopkins University ¹⁴
Martin Pomper, M.D.
mpomper@jhmi.edu ¹⁵

Massachusetts General Hospital ¹⁶
Ralph Weissleder, M.D.
weissleder@helix.mgh.harvard.edu ¹⁷

Vanderbilt University ¹⁸
John C. Gore, Ph.D.
john.gore@vanderbilt.edu ¹⁹

University of California, Los Angeles ²⁰
Michael E. Phelps, Ph.D.
mphelps@mednet.ucla.edu ²¹

Case Western Reserve University ²²
Jeffrey Duerk, Ph.D.
duerk@uhrad.com ²³

University of California at Davis ²⁴
Simon Cherry, Ph.D.
srcherry@ucdavis.edu ²⁵

University of Texas SW Medical Center at Dallas ²⁶
Ralph P. Mason, Ph.D. and Sherry A. Dean, Ph.D.
ralph.mason@utsouthwestern.edu ²⁷

Michigan Small Animal Imaging Resource (MSAIR)
Brian D. Ross, Principle Investigator
University of Michigan

Grant Number: U24CA083099

http://www.med.umich.edu/msair/

The establishment of the Michigan Small Animal Imaging Resource (MSAIR) at the University of Michigan has proved extremely successful. During this time, the MSAIR facility has doubled in overall space and is scheduled to double in size again with a concurrent move to the new Biomedical Science Research Building which will be the focal point of the University of Michigan Medical School. This is part of an expanding Life Sciences Initiative within Michigan which emphasizes collaborative, intellectual innovation and multidisciplinary research. The new facility will also house a state-of-the-art vivarium that has been planned to be integrated together with the MSAIR. Furthermore, the number and types of imaging modalities available for users has dramatically increased during the initial funding of the MSAIR. This includes the addition of a horizontal bore 9.4 tesla MRI system with microgradient coils, addition of two in vivo bioluminescent imaging systems, addition of two microPET systems available for imaging of rodents and monkeys, addition of a fluorescent imaging system and finally, inclusion of a MicroCT system. The number of cancer investigators who have utilized the MSAIR during the initial funding period has also seen remarkable growth (5-fold), thus making an important impact in cancer research.

The objectives of this current project are to: 1) Acquire a combined SPECT/CT device capable of scanning both mice and rats. 2) Recruit a radiochemist to the MSAIR for synthesis of custom PET/SPECT probes. The addition of a radiochemist dedicated to assisting MSAIR users with labeled probes for both PET and SPECT will fulfill a need expressed by many investigators. 3) Provide Core services in molecular biology for the production of custom recombinant protein probes and recombinant cell lines. 4) Initiate a training laboratory and lecture workshop for training investigators in the use of imaging technologies for cancer research.

The overall focus of this proposal is to provide a shared resource and the tools which allow cancer researchers to incorporate state-of-the-art imaging technologies into their individual research interests. Moreover, the MSAIR has become a central, diverse and dynamic resource facility wherein exchange of techniques and ideas can occur, which fosters productive interdisciplinary collaborations in cancer research.

Southwest Small Animal Imaging Resource
John D. Hazle, Ph.D. and Juri Gelovani, M.D., Ph.D.
University of Texas M D Anderson Cancer Center

Grant Number: U24CA126577

Small Animal Imaging Facility ²⁸

This proposal will establish a Small Animal Imaging Research Program (SAIRP) at The University of Texas M. D. Anderson Cancer Center. The proposed SAIRP will complement the existing institutional facility that provides small animal imaging services to NIH funded investigators. The broad goal of this SAIRP is to develop novel imaging approaches to solve cancer related biological questions and evaluate new cancer therapies. Furthermore, the proposed SAIRP will actively develop new small animal imaging projects via collaborations with NIH funded investigators who have not used small animal imaging as a part of their research in the past. The lack of specific funding to introduce animal imaging into these research projects is a serious limitation for inclusion of small animal imaging technologies into their research. Thus, additional funds are requested through the current application to conduct several pilot studies that are aimed at producing convincing preliminary results sufficient for justification of additional funding by the PIs of corresponding projects through their original granting agencies.

The SAIRP is organized into three technology development programs (Instrumentation, Conventional Imaging and Molecular Imaging), seven cores (Instrumentation, Probes & Tracers, Animal Support, Histopathology & Molecular Biology, Computational, Biostatistics, and Administration), and an educational program. The programs work to address the issues of new instrumentation, developing new projects using conventional imaging techniques, and developing new projects using molecular imaging techniques. The cores provide the infrastructure to these programs. Existing imaging modalities include magnetic resonance (MR), x-ray computed tomography, singlephoton nuclear and positron emission tomography (PET). We will add two new optical imaging instruments (Diffuse Optical Tomography and a combined optical/x-ray/gamma scintigraphy device) as our new modality (optical) in Year 1. We will also focus on combining conventional morphologic and physiologic images from the Conventional Imaging Program with metabolic, genetic, and cellular imaging from the Molecular Imaging program through computational processes and refined imaging database. This will allow us to use the most comprehensive and complete imaging datasets for solving the biological questions posed in the Base Grants and New Imaging Projects.

Penn Small Animal Imaging Resource (Penn-SAIR)
Jerry Glickson, Ph.D., and Lewis A. Chodosh, M.D., Ph.D.
University of Pennsylvania

Grant Number: U24CA083105

http://www.uphs.upenn.edu/radiology/depa/SAIF/index.html

A Small Animal Imaging Research program is proposed at U. Penn. (Penn-SAIR) supporting cancer research at Penn, the Wistar Institute, the Children's Hospital of Philadelphia (CHOP), the Lankenau Institute for Medical Research and Thomas Jefferson University; it will be available to other institutions within the Philadelphia region and world-wide. The program builds on a fully self-supported existing Small Animal Research Facility (SAIF).

The SAIF, which came into existence with the termination of previous funding for the SAIRP and Pre-ICMIC programs, serves the needs of Penn as well as the cooperating institutions. It is supported by the Department of Radiology and the Comprehensive Cancer Center, of which it is a core. A complete administrative structure including an Oversight Committee, a Steering Committee, User Committee and an Animal Oversight Committee is already functioning. A Scientific Oversight Committee and Internal and External Advisory Boards would be added to supervise the base projects and imaging technology programs of the proposed SAIR.

The SAIR will serve 4 NIH/DOD funded cancer oriented base projects in years 02-05: 1) Optical and PET imaging of therapeutic response in the hypoxic tumor microenvironment, Wafik S. El-Deiry, MD, PhD, PI; 2) Orthotopic growth and therapy of human melanoma stem cells, Meenhard Herlyn, DVM, PhD, PI, Wistar; 3) Development of PET and optical imaging probes for predicting therapeutic response of non-Hodgkin's lymphoma, Jerry D. Glickson, PhD, PI; 4) Non-invasive imaging of breast cancer progression in inducible transgenic mouse models, Lewis A. Chodosh, MD, PhD, PI; and 4 more projects in years 03-05: 5) Transgenic mice as models for anti-vascular therapy, William M. Lee, MD, PhD, PI; 6) Cancer cell adaptation to metabolic stress, Craig Thompson, MD, PhD, PI; 7) Development of multifunctional nanoparticles for targeting therapeutic DNA delivery and visualization of ovarian metastatic tumors, Janet Sawicki, PhD, PI, Lankenau; and 8) Neuroblastoma biology and therapy: antiangiogenic strategies, John Maris, MD, PhD, PI, CHOP.

The SAIR will support core facilities for NMR (MRI, MRS, and perfused cells), Nuclear Medicine (mPET, mSPECT, mCT), Optical Imaging, Bioluminescence, and Ultrasound with ancillary facilities for Radiochemistry, Chemistry, Molecular Biology, Image Analysis and Animal Tumor Models. Imaging technology developmental programs are proposed in NMR (DCE MRI, lactate/choline imaging, hyperpolarized 13C probes), PET(combined PET/MR/Optical imager), Optical Imaging (tomographic NIR imaging of tumor hypoxia by phosphorescence lifetime measurement), Radiochemistry (development of [18F] ethanolamine as a phospholipid metabolism probe), Chemistry (lipoprotein based iron oxide delivery system, GLUT1 targeted Gd-chelates, NIR molecular beacons for detecting specific phospholipases), and Molecular Biology (peptide nucleic acid based molecular beacons targeting the BRAF V600D,E mutation). A training program for physicians, graduate students, postdocs and technicians is proposed.

Memorial Sloan Kettering Small Animal Imaging Research
Jason A. Koutcher, Principle Investigator
Memorial Sloan-Kettering Cancer Center

Grant Number: U24CA083084

http://www.mskcc.org/mskcc/html/14085.cfm

Research at Memorial Sloan-Kettering Cancer Center is focused on cancer diagnosis and enhancing responses of tumor to treatment with a goal of curing cancer. Animal studies of novel cancer therapeutics, while imperfect as a treatment model, have utility, both in studying therapeutic efficacy and toxicity. Because tumors are heterogenous, both between individuals and within a single tumor, non-invasive imaging studies are necessary to provide information about variation in response.

The main technologies we will focus on include nuclear magnetic resonance (NMR), positron emission tomography (PET), and optical imaging, although other instruments are part of the application. The 3 imaging techniques chosen were based on the fact that they will provide complementary information. NMR imaging provides high spatial resolution but modest functional data. PET and NMR spectroscopy have poorer spatial resolution but provide valuable chemical/metabolic information. Optical imaging can provide very sensitive imaging tools to detect very small numbers of cells and thus these modalities have different strengths. We focus on enhancing the ancillary/support services to maximize information available from the different studies. Image analysis/correlation is important since in most studies, multiple imaging studies are done and it is critical to spatially align different or longitudinal studies. The Synthetic Chemistry and Vector Cores are critical for developing novel tools for exploring signaling pathways, and molecular events related to oncogenesis, treatment, cell death and host toxicity. Enhancement of imaging techniques to maintain state of the art methodologies, improving current techniques, and converting imaging into a more quantitative science is vital.

A wide range of oncologic issues will be studied to exploit these tools in developing newer and better targeted drugs, to minimize host toxicity, to develop standards of response criteria for cytostatic drugs and detect responses/failures earlier in the course of treatment. The range of projects studied include predicting tumor response to treatment, dosimetry for radioimmunotherapy, pharmacology, gene therapy and imaging, tumor metabolism, and evaluating responses to novel cytostatic agents. Research at MSKCC is translational and the goals of many of these projects are to be moved to the clinic in the shortest time feasible.

Leadership will come from the imaging scientists (Drs. Koutcher, Blasberg and Larson) and also from the molecular pharmacology group who will meet monthly along with a Technology Committee, to decide which problems are important and appropriate to be addressed by imaging technology.

Washington University Small Animal Imaging Resource
Joseph J. Ackerman, Principle Investigator
Washington University

Grant Number: U24CA083060

http://www.siteman.wustl.edu/internal.aspx?id=242

The Washington University Small Animal Imaging Resource (WUSAIR), one of the five original Small Animal Imaging Resource Program (SAIRP) centers funded in 1999, provides state-of-the-art facilities and infrastructure for MRI, PET, CT and optical imaging of mice, rats and other small laboratory animals. Located in the heart of the Washington University Medical Center, WUSAIR combines instrumental and intellectual capabilities found at few other institutions. WUSAIR serves a broad community of cancer scientists, non-expert in MRI, CT, PET or optical technology, who have a pressing need for quantitative image analysis of small laboratory animal model systems. A particular focus is on mouse and rat models of cancer. WUSAIR also provides research and development at the frontier of imaging technology in an effort to make the most powerful new imaging strategies available to its community of users.

The ancillary services and capabilities within WUSAIR include physics and engineering support for the development and design of new hardware and imaging methods; informatics support for local and remote data access, analysis, visualization and archival; new contrast agent development; biostatistics consultation for experiment planning and data analysis; and animal procedure assistance for surgical procedures, catheter placement and maintenance and monitoring of physiologic status during imaging experiments. In addition to providing access to and maintenance of MRI, PET, CT and optical small animal scanners and ancillary facilities, WUSAIR services include assistance and training of researchers in small animal imaging procedures and data analysis.

Importantly, WUSAIR is intended to bring imaging expertise fully into the cancer research community by encouraging individuals in collaborating research groups to become competent in hands-on small animal imaging methods. Providing a training center for small animal cancer imaging science extends the impact of WUSAIR beyond that of simply providing imaging services. This training program includes support for a yearly advanced imaging symposium, introductory teaching sessions for local researchers, and technology transfer through multiple-day exchanges of imaging scientists between WUSAIR and other centers of imaging excellence.

Small Animal Imaging Resource Program
G. Allan Johnson, Principle Investigator
Duke University

Grant Number: U24CA092656

http://www.civm.duhs.duke.edu/

We propose the continuation and expansion of the Duke Molecular Imaging Center (DUMIC) as a central element of the Duke Center for In Vivo Microscopy's (CIVM) effort to expand the utility and access of small animal imaging methods for the widest range of cancer researchers.

More specifically, we will do the following: 1. We will integrate all of the Center's activities into the broader imaging initiatives of the University and Medical Center to increase service access for cancer researchers to our existing four MRI, microPET, micro-DSA, micro-CT, micro-ultrasound, and Xenogen optical imaging systems. We will develop high-throughput protocols and deploy a network infrastructure to efficiently design, execute and analyze these small animal imaging protocols. 2. We will extend the capability of our 7.0 T MRI system through a novel slice-selective radial acquisition method to provide higher spatial and contrast resolution along with greater immunity to motion. 3. We will extend the capability of our micro-DSA system (under complementary support from other sources) to provide digital subtraction angiography at spatial resolution down to 20 microns and temporal resolution to 10 ms. 4. We will develop the Molecular Imaging Workbench, a novel, flexible multimodality imaging system that combines micro-CT, digital tomosynthesis for 4D perfusion imaging, and near infrared fluorescent imaging. The system will be constructed in a modular fashion allowing ready extension to other optical imaging methods (GFP, bioluminescence, and micro-SPECT). 5. We will expand our educational program to educate the existing generation of cancer researchers in the potential for small animal imaging. We will reach out across the spectrum.

Small Animal Imaging Resource (SAIR)
Martin G. Pomper, Principle Investigator
Johns Hopkins University

Grant Number: U24CA092871

http://sairp.rad.jhmi.edu/

Small animal imaging is increasingly recognized as an important facet of preclinical and translational cancer research. Perhaps most significant among the clear advantages of imaging experimental animals is that physiology, pathology and novel phenotypes can be understood in the most relevant milieu - in an intact, living system. Less obvious is the fact that often the most significant leap forward that an already important biological study takes is when its results can be extended to the in vivo case - a necessary and often sufficient precondition for success in the clinic. The Johns Hopkins Small Animal Imaging Resource Program (SAIRP) labors to provide that translational step, generating the confidence necessary to move new cancer therapies to patients.

During the next funding period we will continue to complement the already strong magnetic resonance imaging program housed within the In Vivo Cellular and Molecular Imaging Center (ICMIC) with the development of new radiopharmaceutical and optical imaging probes and techniques. We will also expand our mission in several important ways, namely by broadening our educational program to include neighboring institutions, by incorporating elements of industry - focusing on small companies interested in molecular imaging research - and we will offer our expertise in synthetic chemistry and probe development to the SAIRP consortium members who may benefit from it. We will do that while supporting 15 base grants that derive from 3 institutions, but primarily emanate from our own Comprehensive Cancer Center.

Although diverse, the base grants are loosely grouped into 3 themes: targets (reflecting the proliferation of high-throughput target identification methods), cells (due to the many and increasing gene and cell therapy protocols in the Cancer Center) and organs (taking advantage of the SPORE programs and other organ-based cancer research initiatives at Johns Hopkins). We will also continue to serve members of the Cancer Center and elsewhere in less formal ways, providing advice, education, training and pilot data that will further their own cancer research and concurrently enable the SAIRP to become a self-sustaining entity. Our ultimate goal is to move small animal imaging science forward - to the point where the incorporation of such imaging techniques becomes second nature in the daily practice of cancer researchers.

Small Animal Imaging Resource
Ralph Weissleder, M.D., Ph.D., and Umar Mahmood, M.D., Ph.D.
Massachusetts General Hospital

Grant Number: U24CA092782

http://csb.mgh.harvard.edu/mouse_imaging

The overall goal of this U24 application is to continue supporting a team of investigators to develop new and provide established, state-of-the-art high resolution mouse imaging techniques to local cancer investigators. The Harvard Small Animal Imaging Resource (SAIR) has a proven track record for innovation in molecular imaging and clinical translation, has served over 70 regional cancer investigators and currently performs imaging studies for over 40 cancer related base grants. The Program is affiliated with two NCI designated Cancer Centers (the Dana Farber Harvard Cancer Center (DFHCC) and the MIT Center for Cancer Research) and several Mouse Model of Human Cancer Consortia (MMHCC).

The specific goals of the SAIR are to: 1) increase the availability and expand types of high resolution mouse imaging systems, 2) develop new techniques and methods to image cellular and molecular information of specific cancers and organs, 3) assist with image acquisition, 4) maintain and ensure the proper use of imaging equipment, 5) assist in image analysis, processing, quantitation, interpretation and image fusion and 6) provide training to investigators and collaborators with regard to a) small animal handling and monitoring, b) small animal imaging and c) the specifics of utilizing the array of imaging equipment best to address the specific questions at hand. Ancillary cores of this Program include a Pathology, Chemistry, Cell and Bioinformatics Cores. Multidisciplinary training will involve participation in hands-on projects, seminars and didactic lecture series.

The overall focus of this proposal is to provide a shared resource and tools, which allow cancer researchers to incorporate state-of-the-art imaging technologies into their individual research studies. The SAIR has become a dynamic and diverse resource wherein exchange of techniques and ideas occurs rapidly and fosters interdisciplinary collaborations in cancer research.

South-Eastern Center for Imaging Animal Models of Cancer
John C. Gore, Ph.D.
Vanderbilt University

Grant Number: U24CA126588

http://www.vuiis.vanderbilt.edu/

This application seeks support for a new Small Animal Imaging Resource (SAIR) at Vanderbilt University, dedicated to providing scientific and technical resources and support for non-invasive imaging of small animal models of cancer in vivo. The equipment and personnel needed to support cancer imaging in small animals will be provided by a new center which provides access to a comprehensive array of imaging resources.

The center currently allows state-of-the-art studies of small animals in vivo using high field MRI, X-ray CT, optical, ultrasound and nuclear imaging techniques including microPET and microSPECT. This new imaging center is currently housed in 4000 sq ft of space that has been completely renovated to house state-of-the-art instruments. The facility is supported by an expert faculty dedicated to developing new and improved imaging methods and their applications, contiguous laboratory spaces for animal preparation and monitoring, computing resources for image analysis and processing, and an electronics workshop for developing instrumentation and other technical support.

The SAIR would further develop this infrastructure for cancer imaging, and would also advance and integrate new imaging technologies for the comprehensive evaluation and characterization of small animal models of cancer. Specific technological developments would be undertaken in MRI and microSPECT imaging. The SAIR would emphasize combining and integrating the information from different modalities to evaluate specific biological and molecular processes in mouse models. It would develop new imaging instruments and techniques, agents and algorithms to acquire and combine the information obtainable from high field (9.4T, 7T and 4.7T) MRI, novel optical imaging methods, microPET and microSPECT imaging, X-ray CT, ultrasound, imaging mass spectrometry (MALDI), and histology. It would support the development and application of new computer data analyses and image processing methods to combine and correlate these data sets, as well as the provision of a core resource for developing novel targeted contrast agents for each modality.

These capabilities would be applied to several funded research projects, many of which are already using imaging extensively, including studies of specific molecular pathways and mechanisms in transgenic or xenograft mouse models of prostate, hepatocellular, pancreatic, breast, colorectal and skin cancers. The SAIR would be invaluable for supporting ongoing research in tumor biology and molecular imaging within a leading cancer center, and for training of cancer scientists in the applications of imaging methods.

UCLA Imaging Resource for Mouse Cancer Models
Michael E. Phelps, Principle Investigator
University of California, Los Angeles

Grant Number: U24CA092865

http://www.crump.ucla.edu

UCLA has a mature small animal imaging program based on micro-positron emission tomography, x-ray micro computed tomography, in-vivo bioluminescence and digital whole body autoradiography imaging. Central to this program, is our small animal imaging resource (SAIR), which provides service and support through a state of the art facility to more than 24 independent Principal Investigators funded through the NIH and other agencies. Most of the research projects of these investigators are focused in cancer diagnosis and therapy.

In addition to this service component, the roles of the SAIR within the UCLA and the US environments are to: (a) educate students, post-doctoral scholars, physicians and other biology researchers from within and outside UCLA in the tools, technologies and applications of imaging, and (b) foster collaborations and develop new technologies and methodologies that will improve the quantitative capabilities of non-invasive imaging. These goals will hopefully lead to better understanding of human disease and might lead to better methods for diagnosis and treatment of cancer.

As part of this SAIR proposal, besides the research support and education, two developmental projects are included, that should improve the quality and quantitative accuracy of the acquired data, while they reduce the impact from radiation exposure on the studied subjects. The first project will seek to standardize the animal handling and care part of the imaging protocol prior to, during and after the procedure, such that the animal's response is as uniform as possible. The second project seeks to estimate at first, secondly optimize and thirdly track the radiation exposure to the animal subjects throughout sequences of multiple imaging experiments that can last several months. Both these projects will greatly benefit not only the research experiments carried through the UCLA SAIR, but all preclinical research in the US.

Northeastern Ohio Animal Imaging Resource Center (NOAIRC)
Jeffrey L. Duerk, Ph.D. , Principal Investigator
Case Western Reserve University

Grant number: U24 CA110943

http://ccir.uhrad.com/sairc/

In recent years, the development of both small animal models of human cancers as well as technologies for noninvasive imaging via MR imaging and spectroscopy, PET, SPECT, and optical imaging methods (e.g., OCT, bioluminescence, biofluorescence) have created unparalleled opportunities for discovery of the molecular, biological and physiological basis of cancer. The Case Western Reserve University small animal imaging resource program builds on interdisciplinary strengths and ongoing collaborations between cancer biologists, geneticists, pharmacologists, physicists and biomedical engineers to create a unique resource that will serve Northeastern Ohio cancer investigators. We have created a Small Animal Imaging Resource Center (SAIRC) as part of the more comprehensive Case Center for Imaging Research (CCIR) to provide the many regional cancer researchers with state-of-the-art small molecular, cellular and animal imaging. Defined objectives include: 1) development of core resources for quantitative image analysis and multimodality image registration, 2) development of dedicated small animal OCT systems for imaging and color Doppler flow visualization, 3) providing advanced MR imaging and spectroscopy techniques for tracking and assessing efficacy of novel therapeutic agents, 4) create novel imaging agent platforms (e.g., liposomes, micelles, fluorosomes, etc.) that permit functionalization to specific receptors, enzymes or signaling pathways, and when possible to couple these with novel methods for targeted delivery, 5) perform our animal experiments with the highest level of animal welfare support.

Facilities include a combined micro-x-ray computed tomography/SPECT system, a high resolution micro-PET system, bioluminescent/fluorescent imaging capabilities, 7T and 9.4T small animal MR imaging and spectroscopy systems (and a 4T human whole body system for translational studies) from recent grant awards and institutional sources. The SAIRP award allowed us to acquire a bioluminescence/fluorescence imaging system to facilitate development of reporter gene methods and to explore new opportunities in novel agents like quantum dots. Radiopharmaceutical synthesis facilities have also been added. As noted above, we will also create small animal optical coherence tomography with color Doppler and microscopic OCT capabilities to promote in-vivo optical spectroscopic methods and high spatial and temporal examination of structure and function (i.e., perfusion). Rather than focusing on a few specific modalities and determining their potential in cancer research, we focus instead on the biological questions use modalities most amenable to elucidating understanding.

The CCIR/SAIRC provides an integrated environment with core facilities in quantitative image analysis and visualization, novel imaging agents like functionalized liposomes or CEST agents and animal welfare/experiment preparation. The Novel Agents core integrates with our radionuclide imaging capabilities, the ongoing biomolecular and nanoscale engineering for targeted therapeutics initiative at CASE (a.k.a., BioNETT), ongoing research in reporter genes, and a previous P20 In-vivo and Molecular Imaging Center planning grant to add strategic strength in molecular imaging. Interdisciplinary backing for this project is unprecedented with financial and other commitments from three schools of CWRU (Medicine, Engineering, Arts & Sciences), University Hospitals of Cleveland, the Case Comprehensive Cancer Center, and the State of Ohio. All imaging resources and image analysis facilities are located within a new, single 8200 sq. ft. facility to promote cross-collaboration and interdisciplinary research.

UC Davis Mouse Cancer Imaging Program
Simon R. Cherry, Principal Investigator
University of California, Davis

Grant number: U24CA110804

http://imaging.bme.ucdavis.edu/

The UC Davis Mouse Cancer Imaging Program (MCIP) integrates our expertise and resources in small animal imaging and mouse pathology, with our leading cancer researchers, to create new opportunities and directions for studying the basic biology, treatment and prevention of cancer. The MCIP is part of the new Center for Molecular and Genomic Imaging (CMGI), a 4000 sq. ft. dedicated core facility for small-animal imaging located in the Genome and Biomedical Sciences Facility at UC Davis. The CMGI currently has 3 microPET scanners (microPET II, microPET Focus 120, microPET P4), bioluminescence imaging (Xenogen IVIS 100), ultrasound (Siemens Antares with research interface), and 2-D digital fluorescence and autoradiography imaging (Amersham Biosciences Storm 860). As part of the SAIRP, we will be adding microCT capability and adding an upgrade to the Xenogen system to make it capable of in vivo fluorescence imaging. Mouse pathology also forms an integral part of the MCIP and is incorporated through expertise in the UC Davis Mouse Biology Program. The MCIP is enhanced by a range of important ancillary resources, including a biomedical cyclotron (CTI RDS 111) and radiochemistry program, expertise in mouse handling and physiologic monitoring, core laboratories and expertise for creating genetically-engineered mouse models, and support for networking, data handling, databases, and biostatistics.

The MCIP currently supports a range of base grants covering basic cancer biology, mouse models of human cancer, and development and validation of diagnostic and therapeutic agents for novel cancer targets. The MCIP also supports imaging for one of the Mouse Models of Human Cancer Consortium (MMHCC) grants (PI Cory Abate-Shen, UMDNJ). Research projects supported by the MCIP include the development of a fast dynamic CT system for small animal imaging and a low-cost PET scanner for the biology lab. Other components of the MCIP include the development of an extensive database and archiving system for data and image management, and a yearly workshop on small-animal imaging techniques and methods.

The overall goal of the MCIP is to provide cancer researchers at UC Davis and collaborating institutions with the knowledge, support and technology to carry out in vivo imaging studies in mouse models of cancer, and to further develop the technologies and methods for small-animal imaging, including radiotracer and contrast agent development, instrumentation, and quantitative data analysis.

University of Texas Southwestern Small Animal Imaging Resource
Ralph P. Mason, Ph.D., and A. Dean Sherry, Ph.D.
University of Texas Southwestern

Grant Number U24CA126608

Small Animal Imaging Facility in Simmons Cancer Center ²⁹

UT Southwestern Small Animal Imaging Resource ³⁰

We propose to establish the Southwestern Small Animal Imaging Resource (SW-SAIR). This represents a formal structure to promote and facilitate small animal imaging research related to cancer at UT Southwestern. It will use facilities, expertise, and resources of the Department of Radiology, Simmons Comprehensive Cancer Center, and the new Advanced Imaging Research Center. Major recent investment in imaging has provided a new building and substantial infrastructure (instruments, space, and personnel) based on a tripod of collaboration between UT Southwestern Medical Center, UT Dallas and UT Arlington. Based on a Pre-ICMIC, there has been major developing interest in small animal imaging at UT Southwestern. Numerous new grants incorporating or focused on imaging (over $2M), 24 peer-reviewed publications, and multiple new trainees and multiple new collaborations have come to fruition in the past two years alone.

We will initially offer research advice and service in bioluminescent imaging, including our unique multi-head light emission tomography system, MRI and PET based on current instrumentation. To facilitate effective research, we will also have a Reporter Molecule Core to facilitate routine and novel radio labeling and cold chemistry for the development of ligands as reporter molecules. We will also provide support in data analysis and archiving. Our Dean has committed to purchase additional instruments providing SPECT/CT and upgrading the small animal PET and MRI.

The SW-SAIR will have three primary functions i) provide state of the art small animal imaging infrastructure to support a total of 12 Base Grants. These represent Federally funded cancer research including SPORE, PPG and R01 grants with disease sites including lung, brain, prostate, breast and bladder. The grants represent concepts ranging from drug development to tumor physiology to reporter molecule development, ii) research and development to push the frontiers of small animal imaging related to three dimensional bioluminescence and novel molecular targeting agents using the PARACEST approach, and iii) training through an annual symposium, regular seminars and hands-on instruction.

The opening of a new 150, 000 sq ft Advanced Imaging Research Center provides the SW-SAIR access to new state of the art small animal MR, PET, and SPECT/CT facilities as well as space for recruitment of new imaging researchers. The SW-SAIR will not only provide an important regional resource, but will also represent leadership in imaging innovation at the national and international levels.