Overview |
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Atlases of normal mouse development have immense pedagogical value and provide researchers studying normal, mutant, and transgenic mice a standard against which specific examples may be compared and contrasted. Microscopic Magnetic Resonance Imaging (mMRI) provides a means of digitally recording anatomical information in three dimensions from intact specimens at reasonable temporal and spatial resolution. This method can be used to image both fixed and live specimens. Moreover, unique contrast mechanisms can be exploited to highlight different features of the specimens. Standard methods of atlas construction typically involve sacrificing, fixing, sectioning, staining, and then recording photomicrographs of individual sections. Photographic plates are the raw material of most atlases. However, atlases contain two additional critical elements: 1) annotation in the form of graphical reconstructions highlighting important detail, and 2) nomenclature in the form of descriptions and names of discrete structures. The advent of powerful inexpensive computers coupled with the ability to conveniently transport large amounts of data (via CD-ROM or over the Internet) are bringing about changes in the way atlases are constructed and in the ways they can be used. When in book form, the intrinsically three-dimensional animal must be viewed as a series of two-dimensional sections. Moreover, the orientations available to the viewer are limited to samples of standard planes of section (e.g. sagittal, transverse, axial). These restrictions make it difficult to follow complex three-dimensional structures and hinder comparison of one's own 'oblique' sections with the 'orthogonal' sections found in the atlases. Digital atlases have the potential to obviate both of these vexing problems. With the section data reconstructed into three dimensions, highlighting complex structures and computationally sectioning at arbitrary angles becomes possible. Quantitative morphological measurements (volumes, distances, angles) can be accomplished and maps can be generated that amalgamate data from various experimental techniques. Temporal and spatial gene and protein expression patterns, axonal trajectories, patterns of vasculature, and specific neuronal responses to stimuli can all be combined to obtain a canonical organism or system. Such a data set could potentially embody all quantitative information known about the animal in a concise framework.
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The major drawback to classical methods of generating three-dimensional digital atlases is that the specimen must be physically deconstructed from its native three dimensions into a series of two-dimensional sets of data, and then digitally reconstructed back into three dimensions. The reconstruction back into three dimensions is a nontrivial effort because of artifacts generated during histological processing and the computational expense of aligning a host of individual sections. mMRI is a qualitatively different imaging method that offers a convenient means around these difficulties. In the MRI experiment the signal is digitized essentially as it is being originally observed. mMR images are conveniently collected in three dimensions from intact samples with sufficient contrast and spatial resolution to identify many anatomical features. We note that mMRI is a non-invasive/non-destructive imaging technique which allows for single specimen to be analyzed by other methods. | ||||
This project is supported by The Human Brain Project (NIDA and NIMH) and NCRR. |
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