Each year, an estimated 11,000 new spinal cord injuries occur in the United States. The current standard for the evaluation and classification of neurological impairment in adults and children with SCI, the International Standards for Neurological Classification of SCI (ISNCSCI) published by the American Spinal Injury Association (ASIA) have low utility in the pediatric population. This can lead to unreliable assessment of neurological abnormalities in pediatric SCI. The purpose of this project is to establish neuroimaging criteria based on diffusion tensor imaging (DTI) for evaluating the location and severity of spinal cord injury in children and youths among four ASIA Impairment Scale (AIS) classifications (A, B, C/D and E). We will further investigate the test validity by comparing DTI values to ISNCSCI clinical scores, AIS classifications and conventional MRI results. DTI of the spinal cord (SC) is technically limited by various factors, and its use with children has been presumed too challenging. The small cord volume (approximately 1cm in diameter) yields a low Signal-to-Noise Ratio (SNR) and Cerebral Spinal Fluid (CSF) pulsation and blood flow can produce prominent ghosting artifacts and degrade image quality. Recently our imaging group has successfully implemented a high resolution short TE inner FOV (iFoV) neuroimaging DTI imaging method to derive biomarkers sensitive to white matter pathology in pediatric chronic SCI patients. This DTI technique will enable us to collect high resolution DTI images with less distortion and improved SNR making it ideal to image the pediatric spinal cord, and derive biomarkers in an accurate and reproducible manner. Using this method we propose to establish and validate DTI values for the entire spinal cord for normal (25 subjects) and children with spinal cord injuries (75 subjects) among four ASIA Impairment Scale (AIS) classifications (A, B, C/D and E) between the ages of 6 and 21 (Aim#1). High resolution axial MRI imaging (voxel size = 1.2 x 1.2 x 3 mm3) of the spinal cord will be performed using a 3.0T Siemens Verio MR scanner with a 4-channel neck matrix and an 8-channel spine matrix coils. Various DTI values such as FA, MD, AD, and RD obtained from injured cords will be measured and compared to values obtained from uninjured, healthy cords. All the subjects will undergo two identical DTI scans to test for reproducibility and reliability as well as full neurological evaluation based on the ISNCSCI exams. We will evaluate the relationships of DTI values to both the ISNCSCI clinical classifications and conventional MRI to establish DTI measures as imaging biomarker for evaluating severity in pediatric spinal cord (Aim#2). We will also evaluate whether DTI values will be reliable predictors of the precise level of injury compared to ISNCSCI and conventional MRI. Thus, if DTI can be determined to be a valid and reliable method of quantifying viable neural tissue within the injured spinal cord in SCI, it will be a critical neurodiagnostic tool and a useful adjunct to the International Standards of Neurological Classification of Spinal Cord Injury (The Standards).

Public Health Relevance

The current clinical method to evaluate and classify neurological impairment of spinal cord injury (International Standards for Neurological Classification of Spinal Cord Injury) does not have utility in children younger than six years of age, causes anxiety in children up to eight years of age, is difficult to administer (invasive), an does not provide a direct assessment of damage to white matter tracts within the spinal cord. If diffusion tensor imaging (DTI) can be established as a valid and reliable method 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).

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Acute Neural Injury and Epilepsy Study Section (ANIE)
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Jakeman, Lyn B
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Thomas Jefferson University
Schools of Medicine
United States
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Saksena, Sona; Alizadeh, Mahdi; Middleton, Devon M et al. (2018) Characterization of spinal cord diffusion tensor imaging metrics in clinically asymptomatic pediatric subjects with incidental congenital lesions. Spinal Cord Ser Cases 4:41
Alizadeh, Mahdi; Fisher, Joshua; Saksena, Sona et al. (2018) Age related diffusion and tractography changes in typically developing pediatric cervical and thoracic spinal cord. Neuroimage Clin 18:784-792
Alizadeh, Mahdi; Conklin, Chris J; Middleton, Devon M et al. (2018) Identification of ghost artifact using texture analysis in pediatric spinal cord diffusion tensor images. Magn Reson Imaging 47:7-15
Conklin, Chris J; Middleton, Devon M; Alizadeh, Mahdi et al. (2016) Spatially selective 2D RF inner field of view (iFOV) diffusion kurtosis imaging (DKI) of the pediatric spinal cord. Neuroimage Clin 11:61-67