Duchenne muscular dystrophy (DMD) is a progressive degenerative disease that ultimately results in morbidity in the mid-twenties, commonly due to respiratory failure associated with diaphragm muscle degeneration and associated dysfunction. Current measurements of diaphragm function rely on measuring the changes in the along-fiber properties of individual strips of diaphragm tissue in isolation; however, the effects of these changes on overall diaphragm function and breathing ability are not well understood. In order to address this critical gap, the goals of this study are to (i) design a method of measuring in vivo tissue strains both along muscle fibers and transverse to the fiber direction and (ii) use this method to investigate the mechanics of diaphragm function in mdx mice.
Three 6-month-old and two 12-month-old mdx mice were used in this study. A pair of ultrasound crystals was glued to the muscle in the muscle fiber direction, one adjacent to the central tendon and one adjacent to the ribs. A second pair was placed perpendicular to this pair, in the crossfiber direction. The mice were allowed to spontaneously breathe while displacement measurements were taken with a high-resolution sonomicrometry system for 7-10 continuous breaths. Strains were calculated from the measured displacements and compared between age groups.
In this pilot study of 6 and 12-month-old mice, fibers shortened by 2.95%±1.35 and 12.69%±5.95 (respectively) during spontaneous breathing, while the muscle tissue lengthened in the direction perpendicular to the fibers by 4.78%±1.55 and 4.5%±1.81 (respectively). This suggests increased fiber shortening with age. Our method of obtaining in vivo strains was shown to be reliable and repeatable. Future steps include further investigating the changes in dystrophic muscle with age in a larger sample size and comparing the changes seen in dystrophic muscle to those seen in healthy muscle for use in therapy or computational model development.