MULTIPARAMETRIC MRI OF THE PEDIATRIC SPINAL CORD: APPLICATION, DEVELOPMENT, AND QUANTITATIVE MEASUREMENTS OF NORMAL AND PEDIATRIC SUBJECTS WITH SPINAL CORD INJURY

Abstract

Quantitative magnetic resonance imaging (MRI) measurements of the pediatric spinal cord is important for both diagnostic and treatment planning. In recent years several quantitative MRI (qMRI) techniques that have been developed and tested to measure functional and structural information of the spinal cord tissue and microstructure. Several of the existing structural and functional imaging biomarkers (i.e., diffusion tensor imaging (DTI)) have demonstrated potential for providing microstructural information about the spinal cord. However, due to the lack of a standard anatomical template of the pediatric spinal cord, quantification of the spinal cord tissue has been challenging. Therefore, one of the goals of this work is to develop and test tools for quantification as well as the creation of a standard structural template of the typically developing (TD) pediatric spinal cord. This will allow automated measurement of normative values of the spinal cord cross-sectional area (SCCSA) at various levels of the spinal cord. Furthermore, to examine the white matter (WM) microstructure of the pediatric cord we developed a processing pipeline for the atlas-based generation of TD pediatric spinal cord WM tracts. This will facilitate the measurements of normative diffusion values for various WM tracts.A group of 30 TD subjects (age range of 6-17 years old (12.38 ±2.81)), who had no evidence of spinal cord injury or pathology were recruited. We utilized a multiparametric MRI protocol, including high-resolution T2-w structural and diffusion-weighted MRI images to scan the subjects on a 3T MRI scanner. The diffusion data were acquired using a novel iFOV DTI sequence. For quantification, a post-processing pipeline was utilized to generate the structural pediatric template. Next, WM tracts were generated using an atlas-based approach, and diffusion metrics (FA, MD, RD and AD) were quantified in 34 tracts identified in the processing pipeline. Normative SCCSA and DTI diffusion indices were generated for the TD population. Lastly, we demonstrated that DTI indices (i.e. FA) can be a predictive measure of components of the clinical test for spinal cord injury, as well as an indicator of the white matter tracts integrity. Therefore, in the final step of this work, we expanded our quantitative analysis to look at the microstructural and macrostructural changes in 15 children with chronic spinal cord injury (SCI) (AIS A-D, mean age of 12.8 ± 3.1 years). This included measurements of SCCSA, diffusion metrics and T2* WM/GM ratio of various white matter tracts in the patient population. We also examined the relationships between all the metrics and the ISNCSCI clinical scores in SCI subjects. We then compared these measurements between the TD and SCI patients to evaluate the diagnostic utility of these techniques and biomarkers. Statistically significant difference was observed between the two populations in the studied metrics. The results show that the proposed techniques may have the potential to be used as surrogate biomarkers for the quantification of the injured spinal cord. Keywords: diffusion tensor imaging, typically developing, spinal cord injury, spinal cord cross-sectional area, fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity