A computer model of denervation-reinnervation in skeletal muscle.

A computer model of the process of denervation and complete reinnervation of skeletal muscle has been developed for the purpose of exploring underlying mechanisms and for use in the development of new clinical and research tools for evaluating neuromuscular disease. Progressive motor neuron death and reinnervation in this model reproduces the fiber-type grouping, increased fiber density, and minimal increase of motor unit size seen in human chronic denervating diseases. Studies using the model suggest that (1) preferential involvement of motor units of one type could account for the abnormal fiber-type proportions observed in some diseases, (2) reinnervation by axons innervating adjacent fibers is compatible with single fiber multielectrode study results in that it does not produce a large increase in motor unit area, and (3) such reinnervation is sufficient to account for the increases in motor unit density that have been observed. The model has also been used in the development and testing of the Codispersion Index, a measure of the codistribution of two fiber types, which is useful in detecting fiber-type grouping.

Automated system for the analysis of muscle and nerve biopsies.

An automated system has been developed for morphometric analysis of muscle and nerve fibers as seen in routine biopsy tissue preparations. This system, which is suitable both for research and clinical applications, is now in routine use at New England Medical Center Hospital. It is designed around commonly available hardware and uses our own custom software. Special sample preparation is not required, and the system will process almost any biopsy that is free from obvious artifact and suitable for manual assessment. In a typical biopsy, the system provides nearly full automation for the edge (boundary) determination of over 90%of the fibers encountered. An efficient, interactive mode allows for rapid analysis of the remaining 10%. Once fiber boundaries are determined, the system provides fully automatic measurement of the usual parameters such as fiber diameter, as well as a number of parameters not routinely measured with existing manual techniques. Typical analysis times are 35 min for muscle and 2 h for nerve. Complete report generation is provided, with hardcopy available in the pathologist's office. This paper describes the operational aspects of the use of the automated analysis system in routine biopsy work.