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14 November 1996 Mosaic construction, processing, and review of very large electron micrograph composites
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A system of programs is described for acquisition, mosaicking, cueing and interactive review of large-scale transmission electron micrograph composite images. This work was carried out as part of a final-phase clinical analysis study of a drug for the treatment of diabetic peripheral neuropathy. MOre than 500 nerve biopsy samples were prepared, digitally imaged, processed, and reviewed. For a given sample, typically 1000 or more 1.5 megabyte frames were acquired, for a total of between 1 and 2 gigabytes of data per sample. These frames were then automatically registered and mosaicked together into a single virtual image composite, which was subsequently used to perform automatic cueing of axons and axon clusters, as well as review and marking by qualified neuroanatomists. Statistics derived from the review process were used to evaluate the efficacy of the drug in promoting regeneration of myelinated nerve fibers. This effort demonstrates a new, entirely digital capability for doing large-scale electron micrograph studies, in which all of the relevant specimen data can be included at high magnification, as opposed to simply taking a random sample of discrete locations. It opens up the possibility of a new era in electron microscopy--one which broadens the scope of questions that this imaging modality can be used to answer.
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Robert C. Vogt III, John M. Trenkle, and Laurel A. Harmon "Mosaic construction, processing, and review of very large electron micrograph composites", Proc. SPIE 2847, Applications of Digital Image Processing XIX, (14 November 1996);

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