Integrated Center for In Vivo Microscopy

Integrated Center for In Vivo Microscopy

Research Emphasis

The goals of the Integrated Center for In Vivo Microscopy are to develop technologies for small animal imaging and to apply these techniques to important biomedical questions in a broad range of fields such as cancer, toxicology, tumor biology, embryology, histology, neurobiology, stroke, models of pulmonary and heart disease, drug discovery, and molecular biology. The center's integrated team of faculty, staff, and graduate students span a range of disciplines from the biological sciences, engineering, computer science, and physics. Only through integration—understanding the biology, choosing appropriate biomarkers, matching these to the right imaging strategy, and exploiting high-end computational resources—is the highest quality of scientific imaging achieved.

Current Research

Technical developments continue in magnetic resonance (MR) microscopy, micro-positron emission tomography, micro-computed tomography (CT), and micro X-ray imaging. The recent additions of ultrasound and optical methods have expanded the bridge into molecular imaging. Work in hyperpolarized gas continues with the installation of a new specialized high-power laser to increase the polarization efficiency of both ³He and ¹²⁹Xenon. Novel new encoding strategies have been developed to complement the hyperpolarized gas studies, permitting volumetric radial acquisition with effective echo times <200 micro second. The development of non-uniform Fourier encoding is providing increased dynamic range and precision in reconstruction. Three-dimensional Fourier encoding has been expanded to accommodate imaging arrays as large as 4096 x 4096 x 8192.

BIRN

As a partner in the Biomedical Informatics Research Network (BIRN) of NCRR, the center has implemented a state-of-the-art Visual Informatics program providing a searchable database of all of the imaging studies underway in the center. The database ties regulatory, animal metadata, imaging data, and analysis together in a uniform, Web-accessible format. The tools have been constructed to enable imaging across scales from tens of microns for MR microscopy to microns for optical histology, and submicron imaging with electron microscopy.

The scientific focus of the Mouse BIRN is neurodegenerative disease. The center has pioneered the methodology for MR histology, which allows us to routinely acquire 20-micron isotropic images, which we believe are the highest resolution images yet attained in the mouse brain. The methods are being applied to several mouse models at our collaborative institutions—experimental allergic encephalitis (at the University of California, Los Angeles), alphasynuclean model (at the University of California, San Diego), and genetic variations in the BXD mouse (University of Tennessee). More than 200 specimens have been scanned with the protocol to date.

Resource Capabilities

MR microscopes: 2.0 T 30-cm horizontal bore (1-MHz receiver) for in vivo rat and mouse MR imaging and hyperpolarized gas studies; 7.0 T 21-cm horizontal bore (1-MHz receiver) for rat and mouse cardiovascular and neurologic studies; 9.4 T 8.9-cm vertical bore for small animal specimen studies. GE EXCITE consoles control all three of these MR systems. A 7.0 T 21-cm Bruker Advance system was recently installed with special focus on multiple quantum spectroscopy.

Micro-CT/ micro X-ray: Specially developed equipment used for cardiopulmonary imaging can be configured for conventional X-ray or micro-CT and digital subtraction angiography. The system incorporates a Phillips X-ray system and a high-resolution 50-micron X-ray charge-coupled device detector with a custom rotating platform, control system, synchronous ventilator, and micro-injector for contrast.

Hyperpolarized gas: One of only a few Amersham/Nycomed polarizers produces ³He and ¹²⁹Xenon. Pulmonary imaging is supported with precision small animal gas delivery and specialized MRI pulse sequences and reconstruction algorithms.

Micro-PET: A Concorde Microsystems MicroPET R4 small-animal PET scanner is used to study in vivo radiotracer dynamics.

Hardware

Network: More than 120 Silicon Graphics (SGI), Macintosh, LINUX, and personal computer Workstations linked on a switched gigabytes (GB) sec network designed for very large image arrays (currently up to 34 GB/array).

Reconstruction: Three SGI Octane and an SGI Origin 300, 64-bit MIPS R14000 systems configured with fiber channel redundant array of independent disks (RAID).

Workstations: With up to 4 GB of memory, 9 SGI workstations Onyx RE2, Indigo 2 Max Impact, Indigo, and 6 O2), and 12 dual-processor Power Mac G5s provide visualization resources for manipulation, display, reformatting, and three-dimensional volume-rendering and analysis.

Operating systems: IRIX, Linux, Macintosh OS X, Windows XP Professional, Windows 2000, Windows NT, and Solaris.

Image Archives: Two dedicated large image archives comprising 1-terabyte RAID arrays; served by an Oracle database.

Software

Commercial and public-domain software are used.

Scanner control: Pulse sequence programs for high-resolution two-, three-, and four-dimensional imaging.

Image production from raw data: A single tool automatically applies the proper reconstruction method using information stored by the pulse sequence with the raw data. Hardware supports true 64-bit architecture and 64-bit operating systems for large data volumes.

Image storage: An AtlasDB Oracle database stores images along with parameters to describe the subject, scan, and reconstruction techniques. A Web interface provides access to the database.

Visualization: Vitrea medical workstations are used to view and volume-render scans. Other programs include VGStudio Max. Single images and entire volumes are accessible using ImageJ. Other packages include VoxelView, Vitrea, Voxblast, and Amira.

Image analysis: An image pipeline provides volumetric postprocessing, including volumetric T2-weighted contrast, Diffusion Tensor Imaging, and automated segmentation.

Training Opportunities and Workshops

Visit the Center for In Vivio Microspopy training page.

Local: The center's Biomedical Engineering graduate students participate in weekly journal club discussions/seminars that are open to staff, collaborators, the local Duke community, and external collaborators. Visitors to the lab also provide special seminars.

Imaging the rodent workshop: An annual workshop open to the public with participants from Duke, local universities, federal agencies, and pharmaceutical/biomedical industries. Topics cover areas of interest to researchers, focusing on new small animal imaging methods and applications.

MR and CT imaging technology and applications: Held at Kiawah Island Golf Resort, SC. This annual week-long continuing medical education course for radiologists covers topics in MR and CT, such as fast imaging, clinical imaging protocols, angiography, and functional imaging.

In-house training: The center offers collaborators and visitors training sessions to learn about small animal handling and monitoring, operation of MR systems, building radiofrequency coils, and using image processing and advanced visualization tools.

Publications

Visit the Center for In Vivio Microspopy publications page.

1. Badea, C. T., et al., Imaging methods for morphological and functional phenotyping of the rodent heart. Toxicologic Pathology 34:111–117, 2006.

2. Ali, A. A., Dale, A. M., Badea, A., and Johnson, G. A., Automated segmentation of neuroanatomical structures in multispectral MR microscopy of the mouse brain. NeuroImage 27:425–435, 2005.

3. Cyr, M., et al., Magnetic resonance imaging at microscopic resolution reveals subtle morphological changes in a mouse model of dopaminergic hyperfunction. NeuroImage 26:83–90, 2005.

4. Badea, C., Hedlund, L. W., and Johnson, G. A., Micro-CT with respiratory and cardiac gating. Medical Physics 31:3324–3329, 2004.