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.

Public Health Relevance

to Public Health: The current clinical method to evaluate and classify neurological impairment of spinal cord injury (International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI)), causes anxiety in children up to eight years of age, is difficult to administer (invasive), and does not provide a direct assessment of damage to white matter tracts within the spinal cord. The creation of the first pediatric spinal cord structural template, which will be made available to the scientific community, will allow for examination of the spinal cord in a standardized space for group studies and can remove user variability during the analysis process. Also, if functional imaging measures such as DTI, DKI, NODDI, and SCCSA can be established as valid and reliable methods to quantify viable neural tissue within the spinal cord in young children, it will be a critical non invasive neurodiagnostic tool and a useful adjunct to the current ISNCSCI (The Standards).

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS111113-02
Application #
10126066
Study Section
Emerging Imaging Technologies in Neuroscience Study Section (EITN)
Program Officer
Bambrick, Linda Louise
Project Start
2020-03-15
Project End
2025-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
2
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107