title: Brain structural connectivity increases concurrent with functional improvement: evidence from diffusion tensor MRI in children with cerebral palsy during therapy.
abstract: Cerebral Palsy (CP) refers to a heterogeneous group of permanent but non-progressive movement disorders caused by injury to the developing fetal or infant brain (Bax et al., 2005). Because of its serious long-term consequences, effective interventions that can help improve motor function, independence, and quality of life are critically needed. Our ongoing longitudinal clinical trial to treat children with CP is specifically designed to meet this challenge. To maximize the potential for functional improvement, all children in this trial received autologous cord blood transfusions (with order randomized with a placebo administration over 2 years) in conjunction with more standard physical and occupational therapies. As a part of this trial, magnetic resonance imaging (MRI) is used to improve our understanding of how these interventions affect brain development, and to develop biomarkers of treatment efficacy. In this report, diffusion tensor imaging (DTI) and subsequent brain connectome analyses were performed in a subset of children enrolled in the clinical trial (n = 17), who all exhibited positive but varying degrees of functional improvement over the first 2-year period of the study. Strong correlations between increases in white matter (WM) connectivity and functional improvement were demonstrated; however no significant relationships between either of these factors with the age of the child at time of enrollment were identified. Thus, our data indicate that increases in brain connectivity reflect improved functional abilities in children with CP. In future work, this potential biomarker can be used to help differentiate the underlying mechanisms of functional improvement, as well as to identify treatments that can best facilitate functional improvement upon un-blinding of the timing of autologous cord blood transfusions at the completion of this study.
authors.affiliation: Brain Imaging and Analysis Center, Duke University Medical Center, United States ; Department of Biomedical Engineering, Duke University Medical Center, United States.
authors.forename: Zoë A
authors.initials: ZA
authors.lastname: Englander
authors.affiliation: Department of Pediatrics, Duke University Medical Center, United States ; The Robertson Cell and Translational Therapy Center, Duke University Medical Center, United States.
authors.forename: Jessica
authors.initials: J
authors.lastname: Sun
authors.affiliation: Division of Physical Therapy, Duke University Medical Center, United States.
authors.lastname: Laura Case
authors.affiliation: Department of Pediatrics, Duke University Medical Center, United States.
authors.forename: Mohamad A
authors.initials: MA
authors.lastname: Mikati
authors.affiliation: Department of Pediatrics, Duke University Medical Center, United States ; The Robertson Cell and Translational Therapy Center, Duke University Medical Center, United States.
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.affiliation: Brain Imaging and Analysis Center, Duke University Medical Center, United States ; Department of Biomedical Engineering, Duke University Medical Center, United States ; Department of Radiology, Duke University Medical Center, United States.
authors.forename: Allen W
authors.initials: AW
authors.lastname: Song
mesh_terms: D001921:Brain / Q000503:physiopathology*; D002547:Cerebral Palsy / Q000503:physiopathology / Q000534:rehabilitation* / Q000601:surgery; D002675:Child, Preschool; D003131:Combined Modality Therapy; D036101:Cord Blood Stem Cell Transplantation; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007223:Infant; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology*; D026741:Physical Therapy Modalities; D020127:Recovery of Function / Q000502:physiology*
keywords: Cerebral palsy; Diffusion tensor imaging; GMFM-66; Structural connectome