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Small Animal Imaging Core

The Small Animal Imaging Core (SAIC) is directed by Dr. David Colcher and staffed by Dr. James Bading (Imaging Physicist) and Desiree Crow (Core Manager).
 
Preliminary testing in laboratory animals has long had an essential role in the development of new pharmaceuticals and methods for treating human disease. The current development of sophisticated transgenic animal models as well as a growing recognition of the importance of understanding disease processes in the context of the living host has extended the use of animal experimentation beyond safety and efficacy testing into the realm of mechanistic investigation. Non-invasive imaging makes it possible to perform multiple measurements over time in the same animal, thereby enhancing data quality in studies of dynamic molecular and physiologic processes as well as greatly reducing the number of animals required for such studies.
 
During the last several years, scanners for small animals have become commercially available for all of the established modalities of medical imaging (X-ray, CT, MRI, SPECT, PET, ultrasound), as well as for optical imaging. With this technology, the dynamic biodistribution of therapeutic agents as well as vital processes such as gene expression, cell trafficking, cell viability, cell proliferation, tissue hypoxia and angiogenesis can be monitored non-invasively in the intact animal.
 
Small animal imaging has become indispensable to medical research and development and helps the investigator remain competitive for extramural funding.
 
Services
  • Providing consultation to investigators regarding the design, performance and analysis of animal imaging experiments
 
  • Ensuring proper maintenance and calibration of the equipment assigned to the laboratory
 
  • Operating the equipment assigned to the Laboratory or, where appropriate (e.g. for optical imaging equipment), training investigators or their technicians to operate the equipment
 
  • Handling, administering, surveying, tracking and disposing of radioactive materials used in imaging experiments
 
  • Ensuring that all experiments conducted within the Laboratory are performed according to approved protocols
 
Research reported in this publication included work performed in the Small Animal Imaging Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA33572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Equipment

The SAIC currently supports radionuclear, X-ray and fluorescence optical bioluminescence imaging in small animals. Imaging systems in hand include:
 
  • 2 units for optical bioluminescence (IVIS 100, Caliper)
  • 1 unit for fluorescence imaging (IUIS 100, Caliper)
  • 1 gamma camera (g IMAGER; Biospace, Inc.)
  • 1 PET scanner (microPET R4; Siemens)
  • 1 CT scanner (microCAT II Hi-Res; Siemens)
 
The microPET and microCAT are readily used in tandem to generate coregistered functional-anatomic PET/CT images. The Imaging Laboratory is also equipped with a gamma counter (Wallac Wizard 3”; Perkin-Elmer, Inc.).
 
Functional Imaging studies are conducted using a dedicated small animal gamma camera and the microPET system. Engineered antibody constructs (as well as other proteins and peptides) are being labeled with radioiodine (123I/124I) or radiometals (111In/64Cu). Planar imaging studies are being performed using125I- and123I-labeled antibody constructs and/or111In conjugated to the antibody construct using an appropriate chelate linker. The positron emission tomography (PET) studies use124I-labeled antibody constructs as well as64Cu?conjugated to the antibody construct using an appropriate chelate linker (e.g. DOTA), or18F-labeled deoxyglucose or other commercially available compounds labeled with short-lived positron-emitting radioisotopes. Labeled constructs are evaluated in biodistribution and tumor uptake studies in murine xenograft models.
 
Xenogen Biophotonic Imaging Systems
The Xenogen IVIS 100 is a non-invasive, real-time system forin vivoimaging of bioluminescence and fluorescence. In this context, bioluminescence results from enzyme-mediated chemical reactions involving injected substrates. The most commonly used enzyme/substrate combination is luciferase/luciferin. The luciferase gene is incorporated into cells so as to be constitutively (i.e., continuously) expressed for monitoring cellular growth and anatomic location. Alternatively, luciferase may be placed under the control of a promoter of interest and used as a reporter gene. When the animal is injected with luciferin, the luciferase in the cells (e.g. hematopoietic stem cells, tumor, or engineered T-cells) activates the luciferin resulting in the emission of light. Xenogen’s cooled charge-coupled device (CCD) camera system captures the resulting image and allows quantitative analysis of the acquired emissions. These images can be used to monitor cellular activity and track gene expression, the spread of a disease, and the effects of new therapeutics.
   
BiospacegIMAGER
ThegIMAGER is a high-resolution planar scintigraphic camera that combines a customized single 120 mm diameter, 4 mm thick CsI scintillation crystal with a position-sensitive photomultiplier tube to provide to a circular 100 mm diameter field of view. The thickness and composition of the crystal were optimized for use with111In. ThegIMAGER can be used with any of a series of parallel hole collimators designed for the gamma ray emissions of various radioisotopes as well as for various combinations of sensitivity and resolution. We have a collimator designed specifically for imaging mice injected with111In.
   
Small Animal PET Scanner (microPET R4)
The small animal PET scanner (microPET R4) provides fully 3-dimensional PET imaging with spatial resolution of better than 2.0 mm and quantitative accuracy for measurement of tissue activity concentration on the order of 10%. The scanner employs rings of contiguous discrete detectors. The 8 cm axial field of view is adequate for simultaneous whole body imaging of mice. Advanced image reconstruction software is available that provides resolution approaching 1.0 mm. Quantitative accuracy is supported by scatter, dead time and measured attenuation corrections. The system is controlled by a PC running under WINDOWS XT. It includes a fully developed image analysis package that supports volumetric regions of interest and fusion of PET with coregistered anatomic CT or MRI. The microPET system is a powerful instrument for studying thein vivopharmacokinetics, pharmacodynamics and efficacy of novel therapeutic agents.
   
Small-animal CT Scanner (microCAT II Ultra Hi-Res)
The new small-animal CT scanner (microCAT II Ultra Hi-Res) features a continuously tunable source that can provide x-ray peak energies from 20 to 130 kV and spatial resolution ranging from 100 mm down to 15 mm. The scanner is completely self-shielded. Its detector (phosphor screen coupled through a fiber optic light pipe to a CCD chip) is large enough to simultaneously image an entire mouse at low resolution, and the beam can be collimated to prevent exposure of tissues outside the field of interest. The unit is equipped for respiratory gating and has a video camera that enables monitoring of the animal once inside the imaging chamber. The system console is a Windows-based PC. A dedicated image reconstruction engine delivers images in “real-time”, i.e. by the end of scan for image sizes up to 512×512×512 voxels. Images are viewed on a separate, UNIX?based workstation running a powerful suite of image rendering and analysis tools under the AMIRA® package. Of particular importance is the seamless interface between the microCAT and the microPET, which are both from Siemens/CTIMI. The microCAT bed is exchangeable between the two scanners, and the microPET image viewing and analysis package (ASIPro®) supports PET-CT fusion imaging.
 

Small Animal Imaging Core

Small Animal Imaging Core

The Small Animal Imaging Core (SAIC) is directed by Dr. David Colcher and staffed by Dr. James Bading (Imaging Physicist) and Desiree Crow (Core Manager).
 
Preliminary testing in laboratory animals has long had an essential role in the development of new pharmaceuticals and methods for treating human disease. The current development of sophisticated transgenic animal models as well as a growing recognition of the importance of understanding disease processes in the context of the living host has extended the use of animal experimentation beyond safety and efficacy testing into the realm of mechanistic investigation. Non-invasive imaging makes it possible to perform multiple measurements over time in the same animal, thereby enhancing data quality in studies of dynamic molecular and physiologic processes as well as greatly reducing the number of animals required for such studies.
 
During the last several years, scanners for small animals have become commercially available for all of the established modalities of medical imaging (X-ray, CT, MRI, SPECT, PET, ultrasound), as well as for optical imaging. With this technology, the dynamic biodistribution of therapeutic agents as well as vital processes such as gene expression, cell trafficking, cell viability, cell proliferation, tissue hypoxia and angiogenesis can be monitored non-invasively in the intact animal.
 
Small animal imaging has become indispensable to medical research and development and helps the investigator remain competitive for extramural funding.
 
Services
  • Providing consultation to investigators regarding the design, performance and analysis of animal imaging experiments
 
  • Ensuring proper maintenance and calibration of the equipment assigned to the laboratory
 
  • Operating the equipment assigned to the Laboratory or, where appropriate (e.g. for optical imaging equipment), training investigators or their technicians to operate the equipment
 
  • Handling, administering, surveying, tracking and disposing of radioactive materials used in imaging experiments
 
  • Ensuring that all experiments conducted within the Laboratory are performed according to approved protocols
 
Research reported in this publication included work performed in the Small Animal Imaging Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA33572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Equipment

Equipment

The SAIC currently supports radionuclear, X-ray and fluorescence optical bioluminescence imaging in small animals. Imaging systems in hand include:
 
  • 2 units for optical bioluminescence (IVIS 100, Caliper)
  • 1 unit for fluorescence imaging (IUIS 100, Caliper)
  • 1 gamma camera (g IMAGER; Biospace, Inc.)
  • 1 PET scanner (microPET R4; Siemens)
  • 1 CT scanner (microCAT II Hi-Res; Siemens)
 
The microPET and microCAT are readily used in tandem to generate coregistered functional-anatomic PET/CT images. The Imaging Laboratory is also equipped with a gamma counter (Wallac Wizard 3”; Perkin-Elmer, Inc.).
 
Functional Imaging studies are conducted using a dedicated small animal gamma camera and the microPET system. Engineered antibody constructs (as well as other proteins and peptides) are being labeled with radioiodine (123I/124I) or radiometals (111In/64Cu). Planar imaging studies are being performed using125I- and123I-labeled antibody constructs and/or111In conjugated to the antibody construct using an appropriate chelate linker. The positron emission tomography (PET) studies use124I-labeled antibody constructs as well as64Cu?conjugated to the antibody construct using an appropriate chelate linker (e.g. DOTA), or18F-labeled deoxyglucose or other commercially available compounds labeled with short-lived positron-emitting radioisotopes. Labeled constructs are evaluated in biodistribution and tumor uptake studies in murine xenograft models.
 
Xenogen Biophotonic Imaging Systems
The Xenogen IVIS 100 is a non-invasive, real-time system forin vivoimaging of bioluminescence and fluorescence. In this context, bioluminescence results from enzyme-mediated chemical reactions involving injected substrates. The most commonly used enzyme/substrate combination is luciferase/luciferin. The luciferase gene is incorporated into cells so as to be constitutively (i.e., continuously) expressed for monitoring cellular growth and anatomic location. Alternatively, luciferase may be placed under the control of a promoter of interest and used as a reporter gene. When the animal is injected with luciferin, the luciferase in the cells (e.g. hematopoietic stem cells, tumor, or engineered T-cells) activates the luciferin resulting in the emission of light. Xenogen’s cooled charge-coupled device (CCD) camera system captures the resulting image and allows quantitative analysis of the acquired emissions. These images can be used to monitor cellular activity and track gene expression, the spread of a disease, and the effects of new therapeutics.
   
BiospacegIMAGER
ThegIMAGER is a high-resolution planar scintigraphic camera that combines a customized single 120 mm diameter, 4 mm thick CsI scintillation crystal with a position-sensitive photomultiplier tube to provide to a circular 100 mm diameter field of view. The thickness and composition of the crystal were optimized for use with111In. ThegIMAGER can be used with any of a series of parallel hole collimators designed for the gamma ray emissions of various radioisotopes as well as for various combinations of sensitivity and resolution. We have a collimator designed specifically for imaging mice injected with111In.
   
Small Animal PET Scanner (microPET R4)
The small animal PET scanner (microPET R4) provides fully 3-dimensional PET imaging with spatial resolution of better than 2.0 mm and quantitative accuracy for measurement of tissue activity concentration on the order of 10%. The scanner employs rings of contiguous discrete detectors. The 8 cm axial field of view is adequate for simultaneous whole body imaging of mice. Advanced image reconstruction software is available that provides resolution approaching 1.0 mm. Quantitative accuracy is supported by scatter, dead time and measured attenuation corrections. The system is controlled by a PC running under WINDOWS XT. It includes a fully developed image analysis package that supports volumetric regions of interest and fusion of PET with coregistered anatomic CT or MRI. The microPET system is a powerful instrument for studying thein vivopharmacokinetics, pharmacodynamics and efficacy of novel therapeutic agents.
   
Small-animal CT Scanner (microCAT II Ultra Hi-Res)
The new small-animal CT scanner (microCAT II Ultra Hi-Res) features a continuously tunable source that can provide x-ray peak energies from 20 to 130 kV and spatial resolution ranging from 100 mm down to 15 mm. The scanner is completely self-shielded. Its detector (phosphor screen coupled through a fiber optic light pipe to a CCD chip) is large enough to simultaneously image an entire mouse at low resolution, and the beam can be collimated to prevent exposure of tissues outside the field of interest. The unit is equipped for respiratory gating and has a video camera that enables monitoring of the animal once inside the imaging chamber. The system console is a Windows-based PC. A dedicated image reconstruction engine delivers images in “real-time”, i.e. by the end of scan for image sizes up to 512×512×512 voxels. Images are viewed on a separate, UNIX?based workstation running a powerful suite of image rendering and analysis tools under the AMIRA® package. Of particular importance is the seamless interface between the microCAT and the microPET, which are both from Siemens/CTIMI. The microCAT bed is exchangeable between the two scanners, and the microPET image viewing and analysis package (ASIPro®) supports PET-CT fusion imaging.
 
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