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Hippocampal subfields (HCsf) are brain regions important for memory function that are vulnerable to decline with amnestic mild cognitive impairment (aMCI), which is often a preclinical stage of Alzheimer’s disease. Studies in aMCI patients often assess HCsf tissue integrity using measures of volume, which has little specificity to microstructure and pathology. We use magnetic resonance elastography (MRE) to examine the viscoelastic mechanical properties of HCsf tissue, which is related to structural integrity, and sensitively detect differences in older adults with aMCI compared to an age-matched control group. Group comparisons revealed HCsf viscoelasticity is differentially affected in aMCI, with CA1-CA2 and DG-CA3 exhibiting lower stiffness and CA1-CA2 exhibiting higher damping ratio, both indicating poorer tissue integrity in aMCI. Including HCsf stiffness in a logistic regression improves classification of aMCI beyond measures of volume alone. Additionally, lower DG-CA3 stiffness predicted aMCI status regardless of DG-CA3 volume. These findings showcase the benefit of using MRE in detecting subtle pathological tissue changes in individuals with aMCI via the HCsf particularly affected in the disease.

Magnetic resonance elastography (MRE) is a phase contrast MRI technique which uses external palpation to create maps of brain mechanical properties noninvasively and in vivo. These mechanical properties are sensitive to tissue microstructure and reflect tissue integrity. MRE has been used extensively to study aging and neurodegeneration, and to assess individual cognitive differences in adults, but little is known about mechanical properties of the pediatric brain. Here we use high-resolution MRE imaging in participants of ages ranging from childhood to adulthood to understand brain mechanical properties across brain maturation. We find that brain mechanical properties differ considerably between childhood and adulthood, and that neuroanatomical subregions have differing maturational trajectories. Overall, we observe lower brain stiffness and greater brain damping ratio with increasing age from 5 to 35 years. Gray and white matter change differently during maturation, with larger changes occurring in gray matter for both stiffness and damping ratio. We also found that subregions of cortical and subcortical gray matter change differently, with the caudate and thalamus changing the most with age in both stiffness and damping ratio, while cortical subregions have different relationships with age, even between neighboring regions. Understanding how brain mechanical properties mature using high-resolution MRE will allow for a deeper understanding of the neural substrates supporting brain function at this age and can inform future studies of atypical maturation.

Magnetic resonance elastography (MRE) is an MRI technique for imaging the mechanical properties of brain in vivo, and has shown differences in properties between neuroanatomical regions and sensitivity to aging, neurological disorders, and normal brain function. Past MRE studies investigating these properties have typically assumed the brain is mechanically isotropic, though the aligned fibers of white matter suggest an anisotropic material model should be considered for more accurate parameter estimation. Here we used a transversely isotropic, nonlinear inversion algorithm (TI-NLI) and multi-excitation MRE to estimate the anisotropic material parameters of individual white matter tracts in healthy young adults. We found significant differences between individual tracts for three recovered anisotropic parameters: substrate shear stiffness, μ (range: 2.57 – 3.02 kPa), shear anisotropy, φ (range: -0.026 – 0.164), and tensile anisotropy, ζ (range: 0.559 – 1.049). Additionally, we demonstrated the repeatability of these parameter estimates in terms of lower variability of repeated measures in a single subject relative to variability in our sample population. Further, we observed significant differences in anisotropic mechanical properties between segments of the corpus callosum (genu, body, and splenium), which is expected based on differences in axonal microstructure. This study shows the ability of MRE with TI-NLI to estimate anisotropic mechanical properties of white matter and presents reference properties for tracts throughout the healthy brain. Statement of significance: In this study we use magnetic resonance elastography to determine the mechanical properties of white matter, which can be useful in characterizing neurological conditions such as multiple sclerosis and traumatic brain injury. However, due to its fibrous nature, accurate estimation of mechanical properties of white matter requires an anisotropic material model. In this work, we use a transversely isotropic inversion algorithm with data from multi-excitation MRE to determine the anisotropic mechanical properties of white matter in a healthy young population based upon an anisotropic material model. We display the ability of MRE to capture structural differences between different white matter tracts and sub-regions of these tracts, which are expected to reflect differences such as average axon thickness and myelin density. This robust estimation of white matter anisotropic properties in a young, healthy population provides an avenue for future studies to implement these methods to examine brain development, aging, and pathology.

Heightened risk-taking tendencies during adolescence have been hypothesized to be attributable to physiological differences of maturation in key brain regions. The socioemotional system (e.g., nucleus accumbens), which is instrumental in reward response, shows a relatively earlier development trajectory than the cognitive control system (e.g., medial prefrontal cortex), which regulates impulse response. This developmental imbalance between heightened reward seeking and immature cognitive control potentially makes adolescents more susceptible to engaging in risky activities. Here, we assess brain structure in the socioemotional and cognitive control systems through viscoelastic stiffness measured with magnetic resonance elastography (MRE) and volumetry, as well as risk-taking tendencies measured using two experimental tasks in 40 adolescents (mean age ​= ​13.4 years old). MRE measures of regional brain stiffness reflect brain health and development via myelin content and glial matrix makeup, and have been shown to be highly sensitive to cognitive processes as compared to measures of regional brain volume and diffusion weighted imaging metrics. We find here that the viscoelastic and volumetric differences between the nucleus accumbens and the prefrontal cortex are correlated with increased risk-taking behavior in adolescents. These differences in development between the two brain systems can be used as an indicator of those adolescents who are more prone to real world risky activities and a useful measure for characterizing response to intervention.

Viscoelastic mechanical properties of the in vivo human brain, measured noninvasively with magnetic resonance elastography (MRE), have recently been shown to be affected by aging and neurological disease, as well as relate to performance on cognitive tasks in adults. The demonstrated sensitivity of brain mechanical properties to neural tissue integrity make them an attractive target for examining the developing brain; however, to date, MRE studies on children are lacking. In this work, we characterized global and regional brain stiffness and damping ratio in a sample of 40 adolescents aged 12–14 years, including the lobes of the cerebrum and subcortical gray matter structures. We also compared the properties of the adolescent brain to the healthy adult brain. Temporal and parietal cerebral lobes were softer in adolescents compared to adults. We found that of subcortical gray matter structures, the caudate and the putamen were significantly stiffer in adolescents, and that the hippocampus and amygdala were significantly less stiff than all other subcortical structures. This study provides the first detailed characterization of adolescent brain viscoelasticity and provides baseline data to be used in studying development and pathophysiology. Keywords: Magnetic resonance elastography, Brain, Stiffness, Viscoelasticity, Adolescent, Pediatric

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. Keywords: Cerebral palsy, Magnetic resonance elastography, Stiffness, Brain, Pediatric, Viscoelasticity