DTI Tract-Based Quantitative Susceptibility Mapping: An Initial Feasibility Study to Investigate the Potential Role of Myelination in Brain Connectivity Change in Cerebral Palsy Patients During Autologous Cord Blood Cell Therapy Using a Rotationally-Invariant Quantitative Measure

Background: Previous studies using diffusion tensor imaging (DTI)-based connectome analysis revealed improved connectivity in cerebral palsy (CP) patients who underwent autologous umbilical cord blood (UCB) stem-cell therapy. However, the potential mechanism for the connectivity increase remains unclear and needs to be further elucidated. Purpose: To develop a technique with improved accuracy for quantitative susceptibility mapping (QSM) with unique sensitivity to myelin, and demonstrate its use in elucidating the underlying mechanism of the observed motor function improvement and brain connectivity increase in CP patients who received autologous UCB stem-cell therapy. Study Type: Prospective. Population: A cohort of eight pediatric CP patients (2.6 +/- 0.6 years of age) with intact corticospinal tracts (CST) from a randomized, placebo-controlled trial of autologous UCB stem-cell therapy in CP children was included in this study. Field Strength/Sequence: DTI and 3D spoiled gradient recalled (SPGR) QSM at 3.0T. Assessment: Pre- and posttreatment magnetic susceptibility (chi) and the rotationally-invariant magnetic susceptibility anisotropy (MSA) along the CST were derived. Behavioral changes were assessed using the 66-item Gross Motor Function Measurement. Changes in chi and MSA were compared between patients with and without substantial behavioral improvements. Statistical Tests: Two-sample t-tests were performed to assess the differences in the changes of measurements of interest (Delta chi, Delta MSA, and Delta FA) between patients who significantly improved and those who did not. Results: Patients who demonstrated posttreatment motor improvements exceeding expectations showed significantly more diamagnetic Delta chi in the periventricular region along the CST (P = 0.003). Further analysis on the Delta MSA of this region was significantly increased (P = 0.006) for high responders, along with concurrent FA increase. Data Conclusion: These initial findings suggest that the DTI tract-based QSM method has the potential to characterize white matter changes associated with behavioral improvements in CP children who underwent cord blood stem-cell therapy. Technical Efficacy: Stage 2

Automated summary

This study utilized quantitative susceptibility mapping (QSM) to analyze pediatric CP patients who underwent autologous umbilical cord blood stem-cell therapy. The changes in magnetic susceptibility and susceptibility anisotropy along the corticospinal tracts were found to be associated with behavioral improvements, suggesting the potential of QSM in evaluating treatment outcomes for CP children.