Measuring the effects of aging and sex on regional brain stiffness with MR elastography in healthy older adults
Open accessAbstract
Changes in tissue composition and cellular architecture have been associated with neurological disease, and these in turn can affect biomechanical properties. Natural biological factors such as aging and an individual's sex also affect underlying tissue biomechanics in different brain regions. Understanding the normal changes is necessary before determining the efficacy of stiffness imaging for neurological disease diagnosis and therapy monitoring. The objective of this study was to evaluate global and regional changes in brain stiffness as a function of age and sex, using improved MRE acquisition and processing that have been shown to provide median stiffness values that are typically reproducible to within 1% in global measurements and within 2% for regional measurements. Furthermore, this is the first study to report the effects of age and sex over the entire cerebrum volume and over the full frontal, occipital, parietal, temporal, deep gray matter/white matter (insula, deep gray nuclei and white matter tracts), and cerebellum volumes. In 45 volunteers, we observed a significant linear correlation between age and brain stiffness in the cerebrum (P<.0001), frontal lobes (P<.0001), occipital lobes (P=.0005), parietal lobes (P=.0002), and the temporal lobes (P<.0001) of the brain. No significant linear correlation between brain stiffness and age was observed in the cerebellum (P=.74), and the sensory-motor regions (P=.32) of the brain, and a weak linear trend was observed in the deep gray matter/white matter (P=.075). A multiple linear regression model predicted an annual decline of 0.011 ± 0.002 kPa in cerebrum stiffness with a theoretical median age value (76 years old) of 2.56 ± 0.08 kPa. Sexual dimorphism was observed in the temporal (P=.03) and occipital (P=.001) lobes of the brain, but no significant difference was observed in any of the other brain regions (P>.20 for all other regions). The model predicted female occipital and temporal lobes to be 0.23 kPa and 0.09 kPa stiffer than males of the same age, respectively. This study confirms that as the brain ages, there is softening; however, the changes are dependent on region. In addition, stiffness effects due to sex exist in the occipital and temporal lobes.
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In humans, the distinguishing criteria for normal versus pathological aging are CNS injury, amyloid plaques, neurodegeneration, neuropsychiatric conditions, dementia, and impaired performance on cognitive tests.
“In humans, the distinguishing criteria for normal vs pathological aging are: central nervous system (CNS) injury, amyloid plaques (based on positron emission tomography (PET)), neurodegeneration, neuropsychiatric conditions, dementia, and impaired performance on cognitive tests (Arani et al, 2015;Fabbri et al, 2016;Tegeler et al, 2016).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Arani et al, 2015
Aging-associated neuroanatomical changes revealed sexual dimorphism in that males were likely to undergo greater reduction in brain elasticity and stiffness than their female counterparts.
“Aging-associated neuroanatomical changes also revealed sexual dimorphism in that males were likely to undergo greater reduction in brain elasticity and stiffness than their female counterparts (Arani et al, 2015;Sack et al, 2009).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Arani et al, 2015
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McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657 · see citing works
Self-citationAshburner, J., & Friston, K. J. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.02.018 · Cited by 7,507 · see citing works
A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains
Good, C. D., Johnsrude, I. S., Ashburner, J., Henson, R. N. A., Friston, K. J., & Frackowiak, R. S. J. (2001) · NeuroImage · doi:10.1006/nimg.2001.0786 · Cited by 4,561 · see citing works
A meta-analysis of sex differences in human brain structure
Ruigrok, A. N. V., Salimi-Khorshidi, G., Lai, M.-C., Baron-Cohen, S., Lombardo, M. V., Tait, R. J., & Suckling, J. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.12.004 · Cited by 1,192 · see citing works
Normal Sexual Dimorphism of the Adult Human Brain Assessed by In Vivo Magnetic Resonance Imaging
Goldstein, J. M. (2001) · Cerebral Cortex · doi:10.1093/cercor/11.6.490 · Cited by 1,021 · see citing works
Gur, R. C., Turetsky, B. I., Matsui, M., Yan, M., Bilker, W., Hughett, P., & Gur, R. E. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-10-04065.1999 · Cited by 909 · see citing works
Roberts, R. O., Geda, Y. E., Knopman, D. S., Cha, R. H., Pankratz, V. S., Boeve, B. F., Ivnik, R. J., Tangalos, E. G., Petersen, R. C., & Rocca, W. A. (2008) · Neuroepidemiology · doi:10.1159/000115751 · Cited by 796 · see citing works
Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma
Huse, J. T., & Holland, E. C. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2818 · Cited by 765 · see citing works
Why are autism spectrum conditions more prevalent in males?
Baron-Cohen, S., Lombardo, M. V., Auyeung, B., Ashwin, E., Chakrabarti, B., & Knickmeyer, R. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001081 · Cited by 754 · see citing works
Sowell, E. R., Peterson, B. S., Kan, E., Woods, R. P., Yoshii, J., Bansal, R., Xu, D., Zhu, H., Thompson, P. M., & Toga, A. W. (2007) · Cerebral Cortex · doi:10.1093/cercor/bhl066 · Cited by 695 · see citing works
The Young Adult Human Brain: An MRI-based Morphometric Analysis
Filipek, P. A., Richelme, C., Kennedy, D. N., & Caviness, V. S. (1994) · Cerebral Cortex · doi:10.1093/cercor/4.4.344 · Cited by 643 · see citing works
Jack, C. R., Wiste, H. J., Vemuri, P., Weigand, S. D., Senjem, M. L., Zeng, G., Bernstein, M. A., Gunter, J. L., Pankratz, V. S., Aisen, P. S., et al. (2010) · Brain · doi:10.1093/brain/awq277 · Cited by 531 · see citing works
Self-citationAllen, J. S., Bruss, J., Brown, C. K., & Damásio, H. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.05.023 · Cited by 519 · see citing works
The impact of aging and gender on brain viscoelasticity
Sack, I., Beierbach, B., Wuerfel, J., Klatt, D., Hamhaber, U., Papazoglou, S., Martus, P., & Braun, J. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.02.040 · Cited by 423 · see citing works
Sexual dimorphism and asymmetries in the gray–white composition of the human cerebrum
Allen, J. S., Damásio, H., Grabowski, T. J., Bruss, J., & Zhang, W. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00034-x · Cited by 392 · see citing works
Decreased brain stiffness in Alzheimer's disease determined by magnetic resonance elastography
Murphy, M. C., Huston, J., Jack, C. R., Glaser, K. J., Manduca, A., Felmlee, J. P., & Ehman, R. L. (2011) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.22707 · Cited by 349 · see citing works
Self-citationWomen have greater density of neurons in posterior temporal cortex
Witelson, S. F., Glezer, I., & Kigar, D. L. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-05-03418.1995 · Cited by 344 · see citing works
MR-elastography reveals degradation of tissue integrity in multiple sclerosis
Wuerfel, J. T., Paul, F., Beierbach, B., Hamhaber, U., Klatt, D., Papazoglou, S., Zipp, F., Martus, P., Braun, J., & Sack, I. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.06.018 · Cited by 310 · see citing works
Age-Dependent Changes in Material Properties of the Brain and Braincase of the Rat
Gefen, A., Gefen, N., Zhu, Q., Raghupathi, R., & Margulies, S. S. (2003) · Journal of Neurotrauma · doi:10.1089/089771503770802853 · Cited by 299 · see citing works
Brain Viscoelasticity Alteration in Chronic-Progressive Multiple Sclerosis
Streitberger, K., Sack, I., Krefting, D., Pfueller, C. F., Braun, J., Paul, F., & Wuerfel, J. T. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029888 · Cited by 238 · see citing works
Sex Differences in the Brain, Behavior, and Neuropsychiatric Disorders
Bao, A., & Swaab, D. F. (2010) · The Neuroscientist · doi:10.1177/1073858410377005 · Cited by 225 · see citing works
Local mechanical properties of white matter structures in the human brain
Johnson, C. L., McGarry, M., Gharibans, A. A., Weaver, J. B., Paulsen, K. D., Wang, H., Olivero, W. C., Sutton, B. P., & Georgiadis, J. G. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.04.089 · Cited by 199 · see citing works
The Influence of Physiological Aging and Atrophy on Brain Viscoelastic Properties in Humans
Sack, I., Streitberger, K., Krefting, D., Paul, F., & Braun, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023451 · Cited by 190 · see citing works
In vivo viscoelastic properties of the brain in normal pressure hydrocephalus
Streitberger, K., Wiener, E., Hoffmann, J., Freimann, F. B., Klatt, D., Braun, J., Lin, K., McLaughlin, J. R., Sprung, C., Klingebiel, R., et al. (2010) · NMR in Biomedicine · doi:10.1002/nbm.1602 · Cited by 172 · see citing works
Measuring the Characteristic Topography of Brain Stiffness with Magnetic Resonance Elastography
Murphy, M. C., Huston, J., Jack, C. R., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081668 · Cited by 161 · see citing works
Self-citationWitte, A. V., Savli, M., Holik, A., Kasper, S. F., & Lanzenberger, R. R. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.09.046 · Cited by 152 · see citing works
The Pathology of MS: New Insights and Potential Clinical Applications
Pittock, S., & Lucchinetti, C. (2007) · The Neurologist · doi:10.1097/01.nrl.0000253065.31662.37 · Cited by 134 · see citing works
Towards an Elastographic Atlas of Brain Anatomy
Guo, J., Hirsch, S., Fehlner, A., Papazoglou, S., Scheel, M., Braun, J., & Sack, I. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071807 · Cited by 129 · see citing works
In vivo waveguide elastography of white matter tracts in the human brain
Romano, A. J., Scheel, M., Hirsch, S., Braun, J., & Sack, I. (2012) · Magnetic Resonance in Medicine · doi:10.1002/mrm.24141 · Cited by 126 · see citing works
Magnetic resonance elastography of brain tumors: preliminary results
Xu, L., Lin, Y., Han, J. C., Xi, Z. N., Shen, H.-J., & Gao, P. (2007) · Acta Radiologica · doi:10.1080/02841850701199967 · Cited by 125 · see citing works
Viscoelastic properties of human cerebellum using magnetic resonance elastography
Zhang, J. H., Green, M. A., Sinkus, R., & Bilston, L. E. (2011) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2011.04.034 · Cited by 112 · see citing works
Qin, E. C., Sinkus, R., Geng, G., et al. (2012) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.23797 · Cited by 97 · see citing works
Finan, J. D., Elkin, B. S., Pearson, E. M., Kalbian, I. L., & Morrison, B. (2011) · Annals of Biomedical Engineering · doi:10.1007/s10439-011-0394-2 · Cited by 85 · see citing works
Romano, A. J., Guo, J., Prokscha, T., Meyer, T., Hirsch, S., Braun, J., Sack, I., & Scheel, M. (2013) · Magnetic Resonance in Medicine · doi:10.1002/mrm.25067 · Cited by 67 · see citing works
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Guimarães, C. F., Gasperini, L., Marques, A. P., & Reis, R. L. (2020) · Nature Reviews Materials · doi:10.1038/s41578-019-0169-1 · Cited by 1,515 · see citing works
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Niraula, A., Sheridan, J. F., & Godbout, J. P. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.185 · Cited by 398 · see citing works
Grifno, G. N., Farrell, A. M., Linville, R. M., Arevalo, D., Kim, J. H., Gu, L., & Searson, P. C. (2019) · Scientific Reports · doi:10.1038/s41598-019-50193-1 · Cited by 112 · see citing works
Marchini, A., Raspa, A., Pugliese, R., El Malek, M. A., Pastori, V., Lecchi, M., Vescovi, A. L., & Gelain, F. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1818392116 · Cited by 99 · see citing works
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Zorgani, A., Souchon, R., Dinh, A.-H., Chapelon, J.-Y., Ménager, J.-M., Lounis, S., Rouvière, O., & Catheline, S. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1509895112 · Cited by 69 · see citing works
Marangon, D., Caporale, N., Boccazzi, M., Abbracchio, M. P., Testa, G., & Lecca, D. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.748849 · Cited by 34 · see citing works
- Authors
- Arani, A., Murphy, M. C., Glaser, K. J., Manduca, A., Lake, D. S., Kruse, S. A., Jack, C. R., Ehman, R. L., & Huston, J.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Arani, Arvin
- ORCID
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 111
- Pages
- 59-64
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC4387012
- OpenAlex
- W2022224852
- Cited by
- 236
- References
- 34
- Citations by year
- 2026: 18 · 2025: 21 · 2024: 17 · 2023: 27 · 2022: 20 · 2021: 25 · 2020: 22 · 2019: 25 · 2018: 18 · 2017: 18 · 2016: 16 · 2015: 8 · 2014: 1
- FWCI
- 16.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- NeuroImage (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (EB001981, AG16574-14PILOT2)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Ultrasound Imaging and Elastography
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- brain stiffness, magnetic resonance elastography, brain aging, sex differences, cerebrum, cerebellum, brain tissue biomechanics, healthy older adults, sexual dimorphism, cerebral softening, white matter, gray matter, temporal lobe, occipital lobe, frontal lobe, parietal lobe, deep gray matter
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Aging, Biomechanical Phenomena, Cerebellum, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Sex Factors, Cerebrum, Elasticity Imaging Techniques, White Matter, Gray Matter
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