Project Summary Cerebral palsy is the most common movement disorder in childhood and has a profound impact on lifelong musculoskeletal development and function. Children with cerebral palsy often develop an increased resistance to passive range of motion in the affected limbs, particularly prevalent at distal joints such as the wrist, leading to pain, discomfort, and reduced mobility. The underlying structural mechanisms that cause changes in passive biomechanical properties are unknown, but it has been shown that these impairments are progressive over time, resulting in exacerbated function of the affected limbs in adults as compared to children with cerebral palsy. It has been suggested that following the initial brain injury in cerebral palsy, the affected skeletal muscles undergo drastic structural changes that consequently impact biomechanical properties. Thus, I propose to apply a novel approach that integrates innovative in vivo imaging techniques with robust measures of passive joint mechanics to determine the contribution of structural forearm muscle parameters to passive wrist joint properties. Identification of the structural mechanisms underlying deterioration of passive mobility represents the possibility for morphological biomarkers for reduced function in children and adults with cerebral palsy, indicating targets for improved treatment and rehabilitation. The goals of the proposed project are to 1) determine adaptations in muscle structure of the affected limb, and 2) quantify the extent of passive property changes in the paretic limb in children and adults with hemiparetic cerebral palsy. Each aim will have an independent quantitative measurement modality. In Aim 1, magnetic resonance (MR) based diffusion tensor imaging (DTI) techniques will be used to extrapolate fascicle lengths and illustrate changes in the extracellular matrix and intramuscular connective tissue of the paretic forearm muscles. In Aim 2, dynamometry will be used to determine the passive-torque angle relationship at the paretic wrist, giving insight into passive wrist torques (resistance to passive muscle elongation) and passive range of motion. Preliminary work shows that measures of muscle structural adaptations are highly correlated with measures of passive biomechanical properties, indicating promising potential of the proposed research to establish the musculoskeletal underpinnings of progressive motor impairments in individuals with cerebral palsy. Findings from this study will deepen our understanding of the secondary, progressive musculoskeletal impairments that result from a non-progressive neurological injury, specifically evident in cerebral palsy. Furthermore, the proposed research will be critical in informing future research and clinical treatment for the prevention of musculoskeletal impairment exacerbation over the lifespan of individuals with cerebral palsy to improve daily living in this population.