Neurite orientation dispersion and density imaging quantifies corticospinal tract microstructural organization in children with unilateral cerebral palsy

Abstract

Children with unilateral cerebral palsy (UCP) due to early brain injury exhibit disrupted connectivity of corticospinal tracts (CSTs), which can be quantified using diffusion-weighted magnetic resonance imaging (DWI). Diffusion tensor imaging (DTI) is commonly used to quantify white matter organization, however, this model lacks the biological specificity to accurately describe underlying microstructural properties. Newer approaches, such as neurite orientation dispersion and density imaging (NODDI), may provide more biologically accurate information regarding CST microstructure. In this study, we directly compared metrics of CST microstructure using NODDI and DTI models to characterize the microstructural organization of corticospinal pathways. Twenty participants with UCP participating in a neuromodulation/rehabilitation intervention underwent imaging including multi-shell DWI; 10 participants’ datasets were adequately completed for neuroimaging analysis. Task fMRI-guided probabilistic tractography from motor cortex to brainstem was performed at baseline and follow-up to reconstruct the CSTs. Diffusion metrics were compared between hemispheres at baseline, and between baseline and follow-up to test for intervention effects. Correlation analyses were used to compare baseline metrics to changes in hand function following the intervention. DTI results showed that mean fractional anisotropy in lesioned and nonlesioned CSTs did not significantly differ, but mean, axial, and radial diffusivity were greater in the lesioned CST. For NODDI, intracellular volume fraction (ICVF) and orientation dispersion index (ODI) were lower in the lesioned CST. Unimanual function was strongly correlated with ICVF, but not FA. NODDI may reveal distinct properties of CST microstructure that are linked to motor function, indicating their potential in characterizing brain structure and development.

Motor Skill Training May Restore Impaired Corticospinal Tract Fibers in Children With Cerebral Palsy

“…The increase of FA and decrease in MD in the treatment group after HABIT-ILE is consistent with recent pilot studies in children with CP 5,6,27,28 and with results in rodents showing that motor skill learning alters white matter parameters. 29,30 The latter rodent studies showed that motor skill training in the adult led to persistent structural changes in task-relevant white matter pathways that seemed attributable to learning-related increases in myelination.…”

“…Recent small sample pilot studies in children with UCP indicated possible modifications in the anisotropy/number of voxels of CST after training. 5,6,27,28 This observation concurs with modified white matter anisotropy after motor skill training in mice, 29,30 suggesting that CST structure might be restored by intensive motor skill training. Potentially, such changes could be associated with increased myelination produced by newly generated oligodendrocytes.…”

Magnetic Resonance Imaging Correlates of White Matter Gliosis and Injury in Preterm Fetal Sheep Exposed to Progressive Systemic Inflammation

“…In human postmortem tissue, astrocyte numbers contributed to the ODI values on diffusion MRI [46]. Conversely, increased FA and reduced ODI have been attributed to increased axonal thickness and myelination in preterm infants, possibly as part of a compensatory/reparative response to neural injury [47,48]. However, this is not supported by the present study, as there was no change in either the density of myelin or the number of immature and mature (CNPase positive) myelinating oligodendrocytes.…”

Along‐tract statistics of neurite orientation dispersion and density imaging diffusion metrics to enhance MR tractography quantitative analysis in healthy controls and in patients with brain tumors

“…To our knowledge, previous along‐tract studies on WM neurodegeneration in Amyotrophic Lateral Sclerosis (ALS) (Sarica et al, 2017) and MS (Yeatman et al, 2018) only evaluated “classic” DTI metrics, possibly underestimating biologically specific alterations. At the same time, studies exploiting the NODDI model to detect WM anomalies in ALS (Broad et al, 2019), Parkinson's disease (Andica et al, 2018), unilateral cerebral palsy (Nemanich, Mueller, & Gillick, 2019), and stroke (Mastropietro et al, 2019) variously adopted a voxel‐wise or ROI‐based approach to compute the mean of NODDI metrics, possibly underestimating regionally specific alterations. Preliminary results in stroke patients demonstrated the superior specificity of NODDI in detecting subtle WM alterations when compared to FA (Adluru et al, 2014), while studies conducted on MS patients suggested a better detection of spinal cord lesions by means of NODDI rather than DTI‐based analysis (By, Xu, Box, Bagnato, & Smith, 2017).…”