Mechanical Properties of the Cortex: MR Elastography Demonstrates Regional Impacts of Aging and Functional Differences

Introduction:: Aging impacts physical brain integrity, which affects cognition and behavior. Physical degradation of brain tissue manifests as reduction of tissue stiffness and loss of volume [1]. Aging also contributes to a decline in cognitive function, including executive functions supported by the cortex [2], as well as many other functions. Assessing integrity of neural tissue in aging can help elucidate the mechanisms of cognitive decline and monitor response to cognitive rehabilitation. Magnetic resonance elastography (MRE) has been used to non-invasively study changes in the tissue mechanical properties due to its high sensitivity for assessing microstructural tissue health [1]. Previous MRE research has also shown that stiffness of the cerebrum decreases with age [3] and that mechanical properties of brain tissue are linked to both memory and intelligence performance, indicating a so-called viscoelastic structure-function relationship [1]. However, much of this previous work did not examine gray matter of the cortex individually due to its complex geometry and small volume. Recent advancements in MRE methods have addressed these challenges and allow for accurate property recovery of the cortex [4]. This work uses high-resolution MRE to study how aging affects cortical mechanical properties and the mechanical structure-function relationship between MRE and personality, as determined via the five factor personality assessment (NEO).


Materials and Methods:: 57 healthy older adults aged 60 to 85 (69 ± 5.57 years, 18M/39F) completed the MRI session on a Siemens 3T Prisma, with imaging and analysis protocol optimized for cortical property recovery [4]. High resolution MRE data was acquired with 50 Hz vibrations and a total scan time of 10 minutes and 45 seconds [5]. A T₁-weighted MPRAGE was used for segmentation of cortical regions. The 30 bilateral regions were segmented in Freesurfer, converted to binary masks, and subsequently registered in MRE space using FSL FLIRT [6]. A nonlinear inversion algorithm (NLI) was used to estimate the complex shear modulus (G = G’ + iG”) [7]. Storage (G’) and loss moduli (G”) were used to calculate shear stiffness, μ=2|G| / (G’ + |G|) and damping ratio, ξ = G”/2G’. Study participants also completed a 60 question NEO Personality Inventory, which measures the five major domains of personality. We report neuroticism scores for this work because the other factors showed no or very few associations with MRE outcomes. A linear mixed model with repeated measures, controlling for sex and age when appropriate, was used to determine: 1) if shear stiffness differed by region, 2) if there was a significant difference in stiffness with age, 3) if there was a significant difference in stiffness with neuroticism score, and if those relationships differed by region (i.e. interaction). This analysis was repeated for damping ratio. All statistical analyses were performed in SPSS v1.7.


Results, Conclusions, and Discussions:: This study found distinct differences in how material properties varied with age and measures of personality. For stiffness, both age affects (p< 0.001) and regional differences (p< 0.001) were found, as well as a significant regional differences in the stiffness loss with age (p=0.004). Average stiffness decline in the cortical regions, seen in Figure 1, varied from 0.01 to 0.03 kPa/year, with the largest stiffness declines found in the caudal anterior cingulate and caudal middle frontal regions. The stiffness loss across cortical regions is substantially larger than projected stiffness loss in the cerebral lobes and other surrounding tissue [3]. Large age affects were not present in damping ratio. Damping ratio, seen in Figure 2, was significantly different across the regions (p< 0.001) and a significant interaction between neuroticism scores and damping ratio was present (p=0.02), showing a structure-function relationship present in the cortex. Across significant regions, neuroticism scores were shown to increase with elevated damping ratio, consistent with our previous work suggesting higher damping ratio indicates poorer tissue integrity [1]. Taken together, this work shows that mechanical property measures of shear stiffness and damping ratio capture both age affects and the structure-function relationship in the cortex. Shear stiffness, representative of tissue composition, only captured age affects and varied greatly by region. This demonstrates that tracking age-related changes at the whole cortex or the cerebral lobes level would overlook regions with accelerated decline that could be more representative of cognitive deterioration. Measures of tissue stiffness did not relate to the functional measure of personality, instead this was linked to damping ratio, which represents tissue organization. It is notable that personality traits, specifically increased neuroticism, have been identified as a risk factor for neurodegenerative conditions [8]. Overall, this work demonstrates the utility of MRE to study the impacts of aging on the brain and its relationship to cognitive decline, as well as identifies regions of the cortex that are more susceptible to physical degradation.


Acknowledgements (Optional): : This work was funded by the NIH grant R01-AG058853.

References (Optional): : [1] Hiscox, L. V., Schwarb, H., McGarry, M. D. J., and Johnson, C. L., 2021, “Aging Brain Mechanics: Progress and Promise of Magnetic Resonance Elastography,” Neuroimage, 232, p. 117889.

[2] El-Baba, R. M., and Schury, M. P., 2021, “Neuroanatomy, Frontal Cortex,” StatPearls.

[3] Arani, A., Murphy, M. C., Glaser, K. J., Manduca, A., Lake, D. S., Kruse, S. A., Jack, C. R., Ehman, R. L., and Huston, J., 2015, “Measuring the Effects of Aging and Sex on Regional Brain Stiffness with MR Elastography in Healthy Older Adults,” Neuroimage, 111, pp. 59–64.

[4] Hiscox, L. V, McGarry, M. D. J., and Johnson, C. L., 2020, “Mechanical Property Recovery in the Cerebral Cortex Using Magnetic Resonance Elastography,” Proc. Intl. Soc. Mag. Res. Med.

[5] Johnson, C. L., Holtrop, J. L., Anderson, A. T., and Sutton, B. P., 2016, “Brain MR Elastography with Multiband Excitation and Nonlinear Motion-Induced Phase Error Correction,” Proc. Intl. Soc. Mag. Res. Med.

[6] Jenkinson, M., Beckmann, C. F., Behrens, T. E. J., Woolrich, M. W., and Smith, S. M., 2012, “FSL,” Neuroimage, 62(2), pp. 782–790.

[7] Houten, E. E. W. Van, Miga, M. I., Weaver, J. B., Kennedy, F. E., and Paulsen, K. D., 2001, “Three-Dimensional Subzone-Based Reconstruction Algorithm for MR Elastography,” Magn. Reson. Med., 45(5), pp. 827–837.

[8] von Gunten, A., Pocnet, C., and Rossier, J., 2009, “The Impact of Personality Characteristics on the Clinical Expression in Neurodegenerative Disorders—A Review,” Brain Res. Bull., 80(4–5), pp. 179–191.