Duchenne Muscular Dystrophy (DMD) is a common inherited muscle disease showing chronic inflammation and life-limiting progressive weakness of skeletal and cardiac muscle. Absent dystrophin renders sarcolemma more Ca²⁺ permeable, disturbs signaling and triggers inflammation. Sustained degeneration/regeneration cycles render muscle cyto-architecture susceptible to remodeling. Quantitative morphometry was introduced in living cells using multiphoton microscopy (Second Harmonic Generation, SHG) of myosin and image processing. As the time course of cellular remodeling is not known, we used SHG microscopy in toe muscle fibres from mdx mice over a wide age range (<1 to 24 months) for 3D rendering and detection of verniers (local sarcomere lattice disruptions) and cosine angle sums (CAS, measure of force vector variance). Wt and transgenic mice expressing a exD17-48 mini-dystrophin (MinD) were also studied. During maturation, vernier densities declined in wt and MinD fibres until adulthood and stabilized at around 5 mo. In contrast, vernier densities were initially larger in mdx fibres and remained significantly elevated during life span. CAS values were close to unity in adult wt and MinD fibres, in agreement with tight regular myofibril orientation, but somewhat smaller in very young and old mice, probably reflecting maturation and senescent effects. In mdx fibres, CAS were always smaller than in the other groups. Our results give a first detailed morphometric analysis of the dystrophic process regarding cellular remodeling with age. We also provide an improved image algorithm that is optimized for computation time and automation which will be used in future studies in human myopathies.