Measuring the effects of aging and sex on regional brain stiffness with MR elastography in healthy older adults

Abstract

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.

Keywords: Aging; Brain MRE; Brain stiffness; Elastography; Gender bias; Sexual dimorphism.

Figure 1

Plot of median brain stiffness (kPa) versus age in male (blue squares) and female (red circles) populations in the A) cerebrum, B) cerebellum, C) temporal lobes, and D) occipital lobes. Trend lines given by the multiple linear regression model are plotted for males (blue solid line) and females (red solid line). A stiffness versus age-only linear regression line has also been plotted (dashed black line) for comparison purposes.

Figure 2

An example of the overall decrease in cerebrum stiffness observed with aging. Axial anatomical images and elastograms of a 56 (top row) year old and an 89 (bottom row) year old cognitively normal males.

Figure 3

Example elastograms overlaid on the corresponding T1-weighted images of 73 year old age matched male (top row) and female (bottom row) volunteers. The overall stiffness of the occipital lobes appears to be higher in the female volunteer.

Figure 4

Mean median stiffness per decade for all volunteers in the 60–89 year age range. The error bars represent the 95% confidence intervals of the means.