The Mouse Imaging Program (MIP) at the Center for Systems Biology is a uniquely integrated imaging resource providing the larger Harvard/MIT research community with access to state-of-the-art in vivo imaging technologies. The program offers magnetic resonance imaging (MRI), positron emission tomography (PET-CT), single photon emission computed tomography (SPECT-CT), computed tomography (CT), bioluminescence (BLI), fluorescence mediated tomography (FMT), and various other fluorescence imaging technologies. The fully integrated program also provides mouse holding facilities for serial imaging, surgery, anesthesia and veterinary care. Image reconstruction, 3D display, fusion, quantitative image analysis and online data access are also available. The program performs its own research, aimed at continuously improving existing imaging technologies and has deep knowledge of cardiovascular, oncology and neurological mouse models of disease. A list of publications made possible by utilizing MIP resources is available on the Program web site. Imaging requests may be submitted through the MIP website.
"The SPECT system has 2 gamma detectors, which can be equipped with either parallel hole or pinhole collimators, the latter with exchangeable pinhole diameters. The system can be used with various isotopes, most frequently 111In and 99mTc. The spatial resolution for the SPECT system is approximately 1 mm."
"The remarkable feature of this laser scanning (although not confocal) instrument is its unique lenses. Olympus has miniaturized the high performance objective to produce the MicroProbe objective lens, commonly named the "Stick Lens" by researchers. With UIS2 technology, the performance of the MicroProbe lenses are extended into the NIR range (up to 1000nm). Developed in conjunction with the Olympus orthoscopic division, the three lenses have small tips making them well suited to intravital microscopy in whole animals. The lenses are: 6X (0.15NA, 1.3mm tip diameter), 20X (0.5 NA, 1.3 mm diameter, and 27X (0.7NA, 3.0mm diameter). Each lens is a dipping objective and can be inserted directly into tissue. The most important consideration is stabilization of the subject to eliminate vibration due to respiration or heart beat.
The software, based on the FV1000 software, employs 4 laser lines at 488nm, 594nm, 633nm, and 720nm, and the system is able to image multiple fluorescence probes simultaneously. The scan head has a tilting capability to facilitate objective orientation in three dimensions. The three magnifications of the MicroProbe lenses enable users to capture either a large field of view or high resolution images in a living animal. Certain conventional microscope objectives can also be used with the IV110."
The NanoZoomer 2.0-RS is a slide scanner capable of high speed, high sensitivity, and high resolution. Some of its features include:
- Scanning of standard-size (26 mm x 76 mm)
- Slide tray can keep 6 standard-size
- Two scanning modes: x20 (0.46 um/pixel), x40 (0.23 um/pixel)
- Easy-to-use NDP.scan 2.3 scanner software
- High-speed scanning and superb image quality
- Z-stack feature on whole slides allows multilayer scanning at different focal plane of a specimen on a whole slide
- Fluorescence lamp-equipped
"The Olympus OV100 is a hybrid consisting of a planar fluorescent reflectance imaging system, and a high-power microscope system. Multiple filters are available for this system and include green, red, far-red and near-infrared. Images can be captured of whole mice, and the high magnification zoom lens allows for detailed imaging of specific regions of interest. This system is equipped with isoflurane anesthesia and has a heating plate to maintain subject body temperature throughout the course of imaging. "
"The new Siemens Inveon PET-CT (formerly Concord Focus) system uses high light output LSO (Lutetium Oxyorthosilicate) crystals, and has a timing resolution of less than 1.5 nsec, a greater than 10% peak absolute sensitivity, a stationary field of view (FOV) of 12.7 cm (which can increase to 30 cm FOV with continuous bed motion), an energy resolution of less than 18%, over 25,000 individual detector elements, and a spatial resolution of less than 1.4 mm. The CT uses CCD technology that allows the highest available signal-to-noise ratio, and fiber optics that permit the highest efficiency light collection. It has 4,064 x 4,064 detectors, a FOV greater than 10 x 10 cm, a spatial resolution of 15 micron isotropic voxels, and can scan an entire mouse in less than 1 minute. "
The MRI facility within MIP provides high-resolution/high-throughput imaging, using tailored MRI pulse sequences and dedicated RF coils to optimize Signal-to-Noise ratios. Physiological monitoring, including maintenance of body temperature, cardiac and respiratory gating systems are utilized. The magnets provide state-of-the-art high resolution anatomical and functional imaging of various models in cardiovascular, oncology and neuro-research settings, allowing investigations into new molecularly targeted MRI imaging agents.
Under the oversight of the Center for Comparative Medicine at Massachusetts General Hospital, the Program provides mouse housing for serial imaging studies, including housing of BL2 and radioactive animals. Additionally, the Programs mouse rooms allow for bypass of MGH quarantine, thus expediting the start of research projects. The housing rooms are monitored daily by MGH veterinary and husbandry support staffs.
The MIP Core provides surgical services associated with research projects. Services include drug dosing, routine injections, tumor implantations, blood collection and post mortum tissue collection. Additionally, the Core can execute complex surgical procedures, such as surgically-induced myocardial infarctions, tissue isolation for imaging and window chamber implantations. All surgeries are performed in the Cores surgical suite, which is fully equipped for anesthesia, surgical monitoring and recovery.
The IVIS100 bioluminescence imaging system allows for imaging of up to 5 mice at one time.
The MIPortal is an information technology (IT) platform for experimental imaging and is designed to provide researchers with access to archiving and processing of imaging and non-imaging data. Using the tool, DICOM and non-DICOM modalities can be organized, archived, stored and made available via a web browser.
Fluorescence molecular tomography (FMT) allows for detection of fluorescently-labeled cells or agents in vivo using any combination of 4 imaging channels (635/655nm, 680/700nm, 750/780nm, 718/815nm). FMT imaging is typically combined with MRI or CT imaging to create a fused dataset, allowing for anatomical coregistration of fluorescent signal within the body of the mouse.
The Histopathology Platform provides robust ex vivo sectioning, staining and analysis of tissue samples. An Olympus Nanozoomer system allows for digitization of histological slides for detailed quantitative and qualitative analysis.
The Olympus IV110 system allows for cellular resolution imaging of fluorescent agents and cells in vivo.
The MIP imaging core has developed robust methods for utilizing and fusing multimodality image datasets. Through the use of fiducial markers and fusion software (OsiriX and Amira), we can create PET-MRI, FMT-CT, FMT-PET-MRI and other fused datasets both for data analysis as well as publication figures.
In conjunction with the Program's Radiochemistry platform, PET-CT allows for investigations into novel PET imaging agents in the setting of oncology and cardiovascular diseases. Contrast-enhanced imaging facilitates high-resolution anatomical localization of these agents. Dynamic PET-scans, ranging as long as 3 hours are available to study biodistribution in vivo.
Advanced image analysis and processing is available for all projects. We utilize Amira, OsiriX, as well as custom developed Matlab code and other image analysis tools to quantify imaging data.
The Radiochemistry Platform is available to assist in the preparation of novel PET imaging agents through coupling reactions to PET radioisotopes.
SPECT imaging, with or without high-resolution CT scanning, is often used to track radiolabeled cells in vivo in models of cardiovascular disease, neurological diseases and oncology.