Development of an MRI Template & Neuroimaging Biomarkers of the Pediatric Spinal Cord

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The neurological consequence of spinal cord injury (SCI) in children is not fully understood. The inability to accurately assess motor, sensation and extent of injury in the pediatric population raises speculation about diagnoses, recovery potential, and treatment effectiveness. This proposed study builds upon the team's previous work to establish quantitative imaging biomarkers using advanced imaging methods such as diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI) and atrophy estimated through a spinal cord cross sectional area (SCCSA) – in pediatric SCI patients. In the recent years magnetic resonance imaging (MRI) methods such as DTI, DKI, SCCSA measurements, and Neurite Orientation Density Dispersion Imaging (NODDI) have shown promising results as powerful and non-invasive biomarkers to evaluate the spinal cord (SC) in children. To the best of our knowledge, our research team is the only one thus far to apply these imaging techniques to the pediatric population. Although all of these techniques have demonstrated potential for providing microstructural information about the SC, the development and application of objective diffusion- based biomarkers for identifying the precise location of the injured cord has been challenging because neither a standard anatomical template of the pediatric SC nor biological age and sex matched normative values are available. Hence, the first aim of this study is to create a standardized SC imaging template and establish SCCSA measurements of the entire pediatric SC between 6-17 years of age. The second aim of this study will establish normative multishell diffusion imaging values for continuous segments of the cervical-thoracic pediatric SC between 6-17 years of age. This work will result in standardization and consistent interpretation of these neuroimaging metrics and will reduce user variability. A sub aim of this work is to demonstrate the feasibility of these imaging biomarkers in a group of children with chronic motor complete (American Spinal Injury Association Impairment Scale (AIS) A and B) SCI. This work will address a significant knowledge gap by providing functional imaging biomarkers to clinicians and researchers so they can objectively determine the extent of severity and level of injury and develop prediction models in pediatric SCI. This work would also aid clinicians in assessing neurological recovery, and evaluate treatment effectiveness in clinical trials. In addition, these imaging biomarkers and normative templates can be extended to other pediatric SC diseases in the future.