CTSC:MGHresources:The Mouse Imaging Program

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The Mouse Imaging Program (MIP) is a large scale imaging resource supported in part through an NCI U24 grant. The resource provides the larger Harvard/MIT research community with access to state-of-the-art in vivo imaging technologies. The program offers high resolution magnetic resonance (MR), positron emission tomography (PET-CT), single photon emission computed tomography (SPECT-CT), computed tomography (CT), fluorescence mediated tomography (FMT), bioluminescence (BLI), and various other fluorescence imaging technologies. The integrated program also provides mouse holding facilities for serial imaging, surgery, anesthesia, veterinary care and imaging agents. Image reconstruction, 3D display, fusion, quantitative image analysis and server access are also available. The program offers periodic training and performs its own research to continuously improve existing imaging technologies. Imaging requests from investigators of the Mouse Model of Human Cancers Consortia and recipients of NCI grants are prioritized.

• Magnetic Resonance Imaging (MRI)

4.7T and 7T Bruker Pharmascan

The overall goal of the MRI facility is provide high resolution/high throughput imaging capabilities and equipment/pulse sequences that deliver sufficient SNR to test novel molecularly targeted MR imaging agents. Two high field magnets operate at 4.7 Tesla and 7 Tesla fieldstrength, providing the optimal setup to image both T1 and T2/T2* targeting imaging probes. In addition, the magnets facilitate state of the art high resolution anatomical and functional imaging of various mouse models in cancer, cardiovascular and neuro-research. We use tailored MR pulse sequences and high-end, dedicated RF coils, ranging in size from rat whole body to mouse heart, to optimize SNR for specific application. To assure imaging at physiologic conditions and to optimize anesthesia, dedicated monitoring systems are capable of recording the heart and respiratory rate and body temperature, which is kept in a physiological range by MR compatible heating systems.

• PET-CT imaging facility

Siemens Inveon PET-CT

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, greater than 10% peak absolute sensitivity, a stationary 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 min.

GammaMedica X-PET

The imaging system used is Gamma Medica FLEX XPET / XO small animal imaging system. The XPET system has the highest sensitivity and largest axial field of view among small animal PET scanners. The 3D PET system is comprised of 11520 (2.3 mm x 2.38 mm x 10 mm) Bismuth Germanate (BGO) crystals in 48 separate rings. The large axial field of view (11.6 cm) can image an entire mouse with a resolution less than 2 mm.

• SPECT-CT imaging facility

The most recently installed system is a high resolution X-SPECT™ system (Gamma Medica, Northridge, CA, USA). 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 about 1 mm. The CT detector is mounted on the same gantry as the gamma detectors, It has a pixel size of 75 µm and allows the acquisition of a 512x512x512 matrix with reconstruction in about 15 minutes. The CT data can be fused with the SPECT data.

• CT imaging facility

There are three micro-CT systems:

- The first is a part of the Siemens Inveion PET-CT system. It utilizes 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 min.
- The second systems is housed within the XSPECT / XO system. It is a 50 kVp, 1.0 mA, fixed anode and air cooled x-ray tube with a 2 inch by 2 inch (48 um pitch) solid state detector (1024 x 1024 array).
- The third CT system is contained within the XPET / XO system. It has a 80 kVp, 0.6 mA, fixed anode and air cooled x-ray tube with a 4.72 inch by 4.72 inch (50 um pitch) solid state dectector (2048 x 2048 array). The later system is capable of imaging an entire mouse in less than a minute.

• FMT, FPT, MFT imaging facility

FMT imaging

Two FMT systems are available at CMIR to image mice in vivo using a variety of NIR fluorescent imaging agents. The systems are equipped with isoflurane anesthesia and are heated to maintain subject body temperature during imaging. There are 2 fluorescent channels available for imaging (680nm for Cy5.5-like agents and 750nm of AF750-like agents). The FMT software allows for quantification of fluorescence in a 3-dimensional region of interest. While the systems are equipped to capture planar images both in white light and fluorescence, they are also able to detect fluorescence deep within tissue and resolve probe signal in organs such as the lungs and the heart.

Fluorescence Protein Tomography (FPT)

FPT is a variation of FMT that is optimized for the in vivo 3D tomographic imaging of fluorescence proteins in mice. The method expands the everyday fluorescent protein tagging techniques to the 3D non-invasive in-vivo small animal imaging field. The third generation of FPT system is highly versatile. Tomographic imaging can be performed (a) with and without the use of index matching fluid, (b) incorporating a single planar or multiple full-angular projections of the mouse with surface extraction, and (c) multispectral acquisitions with a sequence of filters. The system is equiped with 3 lasers (tunable Ar+, 532nm NdYAG, 593nm DPSS) to excite a wide variety of fluorescent proteins from GFP to the new red shifted fluorescent proteins, and also equiped with the standard 670 and 750 nm diode lasers to excite near infrared fluorescent probes.

Mesoscopic Fluorescence Tomography (MFT)

MFT was developed to operate in the 0.5mm-1cm regime with focus on enabling in-vivo observation of common biological model organisms. The technique utilizes a modified laboratory microscope and multi-projection illumination to collect data at 360-degree projections. It employs the Fermi simplification to the Fokker-Plank solution of the photon transport equation, combined with geometrical optic principles in order to allow in-vivo whole-body visualization of non-transparent three-dimensional structures in samples up to several millimeters in size.

• FRI imaging facility

Olympus OV100

The Olympus OV100 system is a hybrid system of a planar reflectance fluorescent imaging system, and a high-power microscope system. Filters available for this system 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 region of interest. This system is equipped with isoflurane anesthesia and has a heating plate to meintain subject body temperature throughout the course of imaging.

Siemens BonSAI

The Siemens bonSAI system is a fluorescence optical scanner for in vivo imaging of small animals. Consisting of a light source, CCD camera, and light-tight acquisition chamber, it allows for the imaging of one animal at a time and was designed for rapid imaging and ease of use. Filters are available for imaging green ((l max = 447 nm excitation/527 nm emission), red (527 nm excitation/610 nm emission), far red (660 nm excitation/735 nm emission), and near infrared (762 nm excitation/800 nm emission)

CRi Maestro

The CRi Maestro system is designed for multispectral fluorescence-based small animal imaging and analysis in vivo. Included in this system is a light source, CCD camera, and light-tight imaging chamber. The system software allows the elimination of autofluorescence in the desired spectral range, thus improving sensitivity and quantitative accuracy. Excitation/emission filter sets are available for imaging blue (l max = 465 nm excitation/515 nm emission), green (529 nm excitation/580 nm emission), yellow (590 nm exitation/645 nm emission), red (649 nm excitation/700 emission), and far red (690 nm excitation/750 nm emission) fluorophores.

• Bioluminescence imaging (BLI)

CMIR homebuilt system

The bioluminescence imaging system has been designed and assembled at CMIR. It consists of a liquid nitrogen-cooled, photon-counting Roper Scientific CCD in a light tight box, with a large aperture zoom lens for whole animal imaging. The system can operate in single wavelength mode, for typical luciferase experiments, or has (with slightly lower sensitivity) multiwavelength capabilities for near simultaneous imaging of different luminescent constructs.

IVIS system

The CMIR Xenogen IVIS Imaging System 100 consists of a back-illuminated CCD with a closed-cycle refrigeration system, a camera controller, and a light-tight box for bioluminescence imaging. The field of view can be adjusted from 10-25 cm to allow the imaging of two to five mice at a time on a heated platform.