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Topic Name: 3-D microscopic views of tiny mouse brains

Category: Synchrotron Radiation

Research persons: G. Allan Johnson,Anjum Ali-Sharief, Alexandra Badea, Jeffrey Brandenburg, Gary Cofer, Boma Fubara, Sally Gewalt, Laurence Hedlund and Lucy Upchurch

Location: Center for In Vivo Microscopy,Duke University Medical Center,Durham, NC 27710, United States

Details

A multi-institutional consortium including Duke University has created startlingly crisp 3-D microscopic views of tiny mouse brains -- unveiled layer by layer -- by extending the capabilities of conventional magnetic resonance imaging
"These images can be more than 100,000 times higher resolution than a clinical MRI scan," said G. Allan Johnson, Duke's Charles E. Putman Distinguished Professor of radiology and professor of biomedical engineering and physics. He is first author of a report describing the innovations set for publication in the Aug. 1, 2007 issue of the research journal NeuroImage.
Images on the website for Duke's Center for In Vivo Microscopy, which Johnson directs, reveal examples of these innovations in action. In one video two different mouse brains -- one from a normal animal and the other from a rodent missing a gene linked to mental abnormalities -- seem to assemble themselves before the viewer's eyes, structure by structure
After building up like time-lapse photos of opening flowers, the side-by-side brain images begin revolving as overlying tissues dissolve into computer-rendered transparency. What remains visible, seemingly floating over the bases of the animals' skulls, are two color-coded brain structures -- the ventricles and hippocampus -- showing different volumes resulting from specific genetic differences.
Those six schools -- Duke, the California Institute of Technology, the University of Tennessee at Memphis, the University of California at Los Angeles, Drexel College of Medicine and the University of California at San Diego -- are connected via a very high speed network with each other as well as with the San Diego Supercomputing Center
The consortium has developed the computer infrastructure to collect a rapidly growing library of 3-D mouse brain data, and make all the data available on the web. The goal is to use mouse brains as surrogates for human brains to study the connections between genes and brain structure. Investigators from all over the world are sending their models to Duke where the 3-D images are acquired in a standardized fashion and made available via high speed web connections.
High resolution magnetic resonance imaging -- which the researchers call "MRI histology" provides distortion-free 3-D images with superb ability to distinguish subtle tissue differences in the brain, according to Johnson.
The specimen is still actually in the skull," he said. "It hasn't been cut by a knife. It has not been dehydrated and distorted as it would be in conventional histological techniques."
Using computer-guided statistical methods, the data can be segmented into more than 30 anatomical structures with quantitative volume measurements. These structures can then be computer-enhanced to produce color-coded and labeled volume renderings of selected anatomical details in 3-D, seen at any angle.
MRI scanning is also quicker and costs less than conventional histology, he said. MRI histology permits study of an entire brain, which would be prohibitively expensive using conventional methods. The Duke center has pioneered the development of MRI microscopy to image the micro-anatomies of small biological specimens. The NeuroImage study describes the ways his group have devised to manipulate the signals to achieve varieties of contrasts and resolutions.
For instance, the technology can discriminate grey matter from the white matter within mouse brains. "We have the ability to highlight soft tissue differences with extraordinary clarity," Johnson said.
About The Researchers:

G. Allan Johnson, Ph.D.
Director, Center for In Vivo Microscopy; Director, Diagnostic Physics
Interests:
3D imaging, multimedia medical reporting on the net, magnetic resonance microscopy, applications in drug discovery, transgenics, developmental biology toxicology, histology
Office Phone: (919) 684-7754
Email: gaj@orion.mc.duke.edu
Funded:
Under funding from the National Center for Research Resources, the new imaging technologies are being developed and shared by six institutions that form the Mouse Bioinformatics Research Network (MBIRN).
In The Images:
1.Two mouse brains are compared to determine physical changes caused by genetic modifications.
2.These animated micro-CT based images show the moving blood in the left ventricle (LV) of a mouse heart during one heartbeat. The temporal resolution is 10 ms and the spatial resolution is 100 microns on all axes. This 4D segmentation, analysis, and rendering use the Volume Browser (VB) developed by the Pittsburgh Supercomputing Center (PSC). PSC is collaborating with CIVM to extend VB to handle four dimensional data: space plus time, such as these volume series from our micro-CT system and MRM studies of mouse development.
3.3He MR lung imaging
4.a non-invasive micro-CT based imaging technique appropriate for in vivo characterization of cardiac structure and function in mouse models of cardiovascular disease. This prototype micro-CT system addressed two significant barriers to micro-CT in small animals—reduced signal-to-noise imposed by the smaller voxels and motion (C Badea, L. Hedlund, GA Johnson, Micro-CT with respiratory and cardiac gating, Medical Physics 31[12] 3324-3329, 2004; pdf of article). We used high instantaneous X -ray photon fluence with fully integrated monitoring and control of physiologic motion. The micro-CT system with a fixed tube/detector and a rotating specimen. We used a large focal spot (0.3/1 mm) x-ray tube to produce high fluence rates with short exposure times. We optimized the geometry to match focal spot blur with detector pitch and the resolution limits imposed by the reproducibility of gating. Thus, it is possible to achieve isotropic spatial resolution of 100 microns with a fluence rate at the detector 250-times that of a conventional cone beam micro-CT system with rotating detector and microfocal x-ray tube. Motion is minimized for any single projection with 10 ms exposures that are synchronized to cardiac and breathing motion.
5.Brain slices can also be computer-combined into labeled 3-D anatomical renderings | Center for In Vivo Microscopy