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 has 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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Purpose To noninvasively evaluate gliomas with magnetic resonance elastography (MRE) to characterize the relationship of tumor stiffness with tumor grade and mutations in the IDH1 gene. Materials and Methods With institutional review board approval and following written, informed consent, tumor stiffness properties were prospectively quantified in 18 patients (mean age 42, 6 female) with histologically proven gliomas using MRE from 2014–2016. Images were acquired on a 3T MR unit with a vibration frequency of 60 Hz. Tumor stiffness was compared with unaffected contralateral white matter, across tumor grade and by IDH1 mutation status. The performance of the use of tumor stiffness to predict tumor grade and IDH1 mutation was evaluated by using Wilcoxon rank sum, one-way ANOVA and Tukey-Kramer tests. Results Gliomas were softer than healthy brain parenchyma, 2.2 kPa compared to 3.3 kPa (p < .0001) with grade IV tumors softer than grade II. Tumors with an IDH1 mutation were significantly stiffer than those with wild-type IDH1, 2.5 kPa vs. 1.6 kPa respectively (p = .007). Conclusions MRE demonstrated that gliomas were not only softer than normal brain but the degree of softening was directly correlated with tumor grade and IDH1 mutation status. Noninvasive determination of tumor grade and IDH1 mutation may result in improved stratification of patients for different treatment options and the evaluation of novel therapeutics. This work reports on the emerging field of mechanogenomics – the identification of genetic features such as IDH1 mutation using intrinsic biomechanical information.

Altered iron metabolism has been hypothesized to be associated with Alzheimer’s disease pathology, and prior work has shown associations between iron load and beta amyloid plaques. Quantitative susceptibility mapping (QSM) is a recently popularized MR technique to infer local tissue susceptibility secondary to the presence of iron as well as other minerals. Greater QSM values imply greater iron concentration in tissue. QSM has been used to study relationships between cerebral iron load and established markers of Alzheimer’s disease, however relationships remain unclear. In this work we study QSM signal characteristics and associations between susceptibility measured on QSM and established clinical and imaging markers of Alzheimer’s disease. The study included 421 participants (234 male, median age 70 years, range 34–97 years) from the Mayo Clinic Study of Aging and Alzheimer’s Disease Research Center; 296 (70%) had a diagnosis of cognitively unimpaired, 69 (16%) mild cognitive impairment, and 56 (13%) amnestic dementia. All participants had multi-echo gradient recalled echo imaging, PiB amyloid PET, and Tauvid tau PET. Variance components analysis showed that variation in cortical susceptibility across participants was low. Linear regression models were fit to assess associations with regional susceptibility. Expected increases in susceptibility were found with older age and cognitive impairment in the deep and inferior gray nuclei (pallidum, putamen, substantia nigra, subthalamic nucleus) (betas: 0.0017 to 0.0053 ppm for a 10 year increase in age, p = 0.03 to < 0.001; betas: 0.0021 to 0.0058 ppm for a 5 point decrease in Short Test of Mental Status, p = 0.003 to p < 0.001). Effect sizes in cortical regions were smaller, and the age associations were generally negative. Higher susceptibility was significantly associated with higher amyloid PET SUVR in the pallidum and putamen (betas: 0.0029 and 0.0012 ppm for a 20% increase in amyloid PET, p = 0.05 and 0.02, respectively), higher tau PET in the basal ganglia with the largest effect size in the pallidum (0.0082 ppm for a 20% increase in tau PET, p < 0.001), and with lower cortical gray matter volume in the medial temporal lobe (0.0006 ppm for a 20% decrease in volume, p = 0.03). Overall, these findings suggest that susceptibility in the deep and inferior gray nuclei, particularly the pallidum and putamen, may be a marker of cognitive decline, amyloid deposition, and off-target binding of the tau ligand. Although iron has been demonstrated in amyloid plaques and in association with neurodegeneration, it is of insufficient quantity to be reliably detected in the cortex using this implementation of QSM.

Background and Purpose To investigate age-corrected brain Magnetic Resonance Elastography findings in four dementia cohorts: Alzheimer’s disease, dementia with Lewy bodies, frontotemporal dementia and normal pressure hydrocephalus; and determine the potential use as a differentiating biomarker in dementia subtypes. Materials and Methods Institutional Review Board approval and written informed consent was obtained to perform Magnetic Resonance Elastography on 84 subjects: 20 normal pressure hydrocephalus patients; 8 Alzheimer’s disease patients; 5 dementia with Lewy bodies patients; 5 frontotemporal dementia patients; and 46 cognitively normal controls. Shear waves of 60 Hz vibration frequency were transmitted into the brain using a pillow-like passive driver, and brain stiffness was determined in eight different regions (cerebrum, frontal, occipital, parietal, temporal, deep grey matter/white matter, sensorimotor cortex and cerebellum). All stiffness values were age-corrected and compared with normal controls. The Wilcoxon rank sum test and linear regression were used for statistical analysis. Results Regional stiffness patterns unique to each dementing disorder were observed. Alzheimer’s disease and frontotemporal dementia patients showed decreased cerebral stiffness (p=0.001 and p=0.002 respectively), with regional softening of the frontal and temporal lobes. Alzheimer’s disease patients additionally showed parietal lobe and sensorimotor region softening (p=0.039 and p=0.018 respectively). Normal pressure hydrocephalus patients showed stiffening of the parietal, occipital and sensorimotor regions (p=0.007, p<0.001, and p<0.0001 respectively). Dementia with Lewy bodies patients did not show significant stiffness changes in any of the regions. Conclusion Quantitative Magnetic Resonance Elastography of changes in brain viscoelastic structure demonstrates unique regional brain stiffness patterns between common dementia subtypes.