Altered brain tissue viscoelasticity in pediatric cerebral palsy measured by magnetic resonance elastography

Abstract

Cerebral palsy (CP) is a neurodevelopmental disorder that results in functional motor impairment and disability in children. CP is characterized by neural injury though many children do not exhibit brain lesions or damage. Advanced structural MRI measures may be more sensitively related to clinical outcomes in this population. Magnetic resonance elastography (MRE) measures the viscoelastic mechanical properties of brain tissue, which vary extensively between normal and disease states, and we hypothesized that the viscoelasticity of brain tissue is reduced in children with CP. Using a global region-of-interest-based analysis, we found that the stiffness of the cerebral gray matter in children with CP is significantly lower than in typically developing (TD) children, while the damping ratio of gray matter is significantly higher in CP. A voxel-wise analysis confirmed this finding, and additionally found stiffness and damping ratio differences between groups in regions of white matter. These results indicate that there is a difference in brain tissue health in children with CP that is quantifiable through stiffness and damping ratio measured with MRE. Understanding brain tissue mechanics in the pediatric CP population may aid in the diagnosis and evaluation of CP.

Brain Stiffness Relates to Dynamic Balance Reactions in Children With Cerebral Palsy

“…Children at this low level of impairment may frequently have little or no discernable motor impairment while doing daily activities. However, we have used magnetic resonance elastography previously to observe significant differences in brain stiffness between the same group of children with cerebral palsy at Gross Motor Function Classification System level 1 and 2 compared with typically developing children, 31 indicating sensitivity of stiffness to brain health in this population, and significant correlations between brain stiffness and balance in children with cerebral palsy are again reported here. The 2 largest clusters where stiffness correlated with anterior single-stepping threshold were centered on the right superior temporal gyrus and the left middle temporal gyrus, though these clusters are large and span 4091 voxels and 1449 2-mm isotropic voxels, respectively.…”

“…29,30 We previously performed the first study of brain stiffness in children with cerebral palsy using magnetic resonance elastography and found that global gray matter stiffness, as well as local regions of gray and white matter, were significantly less stiff in children with cerebral palsy than in typically developing children. 31 This study provided the first evidence that brain mechanical properties are affected in cerebral palsy, indicating reduced structural integrity of neural tissue in this population. Our next goal is to determine how these altered brain properties may relate to neuromuscular function.…”

“…Indeed, in this population we previously observed differences in the stiffness of the precentral gyrus between cerebral palsy and typically developing children. 31 The cuneus and precuneus each reside at the center of clusters associated with anterior SST. Interestingly, these are 2 regions where stiffness is inversely related to balance performance.…”

“…The magnetic resonance elastography data in this analysis is the same as previously collected by our group to compare brain viscoelasticity of children with cerebral palsy, ages 5-12, with typically developing children. 31 Of the 12 children with cerebral palsy who participated in that study, 10 (6 girls, 4 boys; mean age ¼ 8.6 + 1.9 years; mean body mass index ¼ 16.7 + 1.5) additionally completed a set of functional assessments as part of a separate study. Participants were recruited through the orthopedic surgery clinic at Nemours/A.I.…”

“…An estimation of the false discovery rate, 50 which is a common technique used for multiple hypothesis testing, was found and all voxels with a false discovery rate >0.05 were excluded so that each voxel has at most a 5% chance of being a false positive. This pipeline is similar to that of the voxel-wise comparison between cerebral palsy and typically developing brain stiffness used by Chaze et al 31 The anatomical locations of the centers of these regions were identified by the MNI coordinates. We only considered clusters with at least 200 significant adjacent voxels; this large cluster size was chosen to account for the inherent smoothing in magnetic resonance elastography property maps and still be larger than the expected point spread function of the nonlinear inversion processing.…”