Diffusion Kurtosis Imaging of the neonatal Spinal Cord: design and application of the first processing pipeline implemented in Spinal Cord Toolbox

Abstract Diffusion Kurtosis Imaging (DKI) has undisputed advantages over more classical diffusion Magnetic Resonance Imaging (dMRI), as witnessed by a fast-increasing number of clinical applications and software packages widely adopted in brain imaging domain. Despite its power in probing tissue microstructure compared to conventional MRI, DKI is still largely underutilized in Spinal Cord (SC) imaging because of its inherently demanding technological requirements. If state-of-the-art hardware advancements have recently allowed to make great strides in applying this emerging method to adult and child SC, the same does not apply to neonatal setting. Indeed, amplified technical issues related to SC district in this age range have made this field still unexplored. However, results arising from recent application of DKI to adult and child SC are promising enough to suggest how informative this technique would be in investigating newborns, too. Due to its extreme sensitivity to non-gaussian diffusion, DKI proves particularly suitable for detecting complex, subtle, fast microstructural changes occurring in this area at this early and critical stage of development, and not identifiable with only DTI. Given the multiplicity of congenital anomalies of the spinal canal, their crucial effect on later developmental outcome, and the close interconnection between SC region and the above brain, managing to apply such a method to neonatal cohort becomes of utmost importance. In this work, we illustrate the first semi-automated pipeline for handling with DKI data of neonatal SC, from acquisition setting to estimation of diffusion (DTI & DKI) measures, through accurate adjustment of processing algorithms customized for adult SC. Each processing step of this pipeline, built on Spinal Cord Toolbox (SCT) software, has undergone Quality Control check by supervision of an expert pediatric neuroradiologist, and the overall procedure has preliminarily been tested in a pilot clinical case study. Results of this application agree with findings achieved in a corresponding adult survey, thus confirming validity of adopted pipeline and diagnostic value of DKI in pediatrics. This novel tool hence paves the wave for extending its application also to other promising advanced dMRI models, such as Neurite Orientation Dispersion and Density Imaging (NODDI), and to a wider range of potential clinical applications concerning neonatal period.