A computational pipeline towards large-scale and multiscale modeling of traumatic axonal injury.

Contemporary biomechanical modeling of traumatic brain injury (TBI) focuses on either the global brain as an organ or a representative tiny section of a single axon. In addition, while it is common for a global brain model to employ real-world impacts as input, axonal injury models have largely been limited to inputs of either tension or compression with assumed peak strain and strain rate. These major gaps between global and microscale modeling preclude a systematic and mechanistic investigation of how tissue strain from impact leads to downstream axonal damage throughout the white matter. In this study, a unique subject-specific multimodality dataset from a male ice-hockey player sustaining a diagnosed concussion is used to establish an efficient and scalable computational pipeline. It is then employed to derive voxelized brain deformation, maximum principal strains and white matter fiber strains, and finally, to produce diverse fiber strain profiles of various shapes in temporal history necessary for the development and application of a deep learning axonal injury model in the future. The pipeline employs a structured, voxelized representation of brain deformation with adjustable spatial resolution independent of model mesh resolution. The method can be easily extended to other head impacts or individuals. The framework established in this work is critical for enabling large-scale (i.e., across the entire white matter region, head impacts, and individuals) and multiscale (i.e., from organ to cell length scales) modeling for the investigation of traumatic axonal injury (TAI) triggering mechanisms. Ultimately, these efforts could enhance the assessment of concussion risks and design of protective headgear. Therefore, this work contributes to improved strategies for concussion detection, mitigation, and prevention.