Electrical pathways through the intricate network of skeletal muscle fibres

Objective: Skeletal muscles exhibit pronounced anisotropy due to their highly oriented fibre structure, a property that significantly influences the spatial distribution of tissue mechanical and electrical properties. Understanding this anisotropy is critical for advancing biomedical applications such as electrical stimulation, bioelectric impedance analysis, and novel therapeutic interventions such as pulsed field ablation (PFA). Methods: We developed a numerical model incorporating realistic skeletal muscle fibre geometry at the microscale to elucidate the origins of the experimentally observed anisotropy at the bulk tissue level. To validate the model, we evaluated the skeletal muscle anisotropy using current density imaging (CDI), a magnetic resonance-based technique. Results: The developed numerical model identifies the origins of the observed anisotropy in bulk tissue. Experimental CDI measurements validate the model, confirming that the observed current anisotropy arises from the intrinsic properties of individual muscle fibres and their organization within the tissue. Remarkably, this anisotropy persists several – even up to 48 – hours post-mortem, suggesting a structural basis that transcends the level of muscle cell membranes. Conclusion: The integration of CDI with advanced modelling provides a powerful framework for understanding and leveraging skeletal muscle anisotropy in both imaging and therapeutic applications. Significance: Our study provides an experimentally validated model of skeletal muscle that is relevant to biomedical applications involving electrical treatments. It also invites further experimentation using tissues immediately after harvesting, demonstrating potential use of ex vivo tissues as models of in vivo tissue, reducing the need for experimentation with live animals and the associated ethical burden.