Mechanical property alterations across the cerebral cortex due to Alzheimer’s disease

Abstract

Alzheimer’s disease is a personally devastating neurodegenerative disorder and a major public health concern. There is an urgent need for medical imaging techniques that better characterize the early stages and monitor the progression of the disease. Magnetic resonance elastography (MRE) is a relatively new and highly sensitive MRI technique that can non-invasively assess tissue microstructural integrity via measurement of brain viscoelastic mechanical properties. For the first time, we use high-resolution MRE methods to conduct a voxel-wise MRE investigation and state-of-the-art post hoc region of interest analysis of the viscoelastic properties of the cerebral cortex in patients with Alzheimer’s disease (N = 11) compared with cognitively healthy older adults (N = 12). We replicated previous findings that have reported significant volume and stiffness reductions at the whole-brain level. Significant reductions in volume were also observed in Alzheimer’s disease when white matter, cortical grey matter and subcortical grey matter compartments were considered separately; lower stiffness was also observed in white matter and cortical grey matter, but not in subcortical grey matter. Voxel-based morphometry of both cortical and subcortical grey matter revealed localized reductions in volume due to Alzheimer’s disease in the hippocampus, fusiform, middle, superior temporal gyri and precuneus. Similarly, voxel-based MRE identified lower stiffness in the middle and superior temporal gyri and precuneus, although the spatial distribution of these effects was not identical to the pattern of volume reduction. Notably, MRE additionally identified stiffness deficits in the operculum and precentral gyrus located within the frontal lobe; regions that did not undergo volume loss identified through voxel-based morphometry. Voxel-based-morphometry and voxel-based MRE results were confirmed by a complementary post hoc region-of-interest approach in native space where the viscoelastic changes remained significant even after statistically controlling for regional volumes. The pattern of reduction in cortical stiffness observed in Alzheimer’s disease patients raises the possibility that MRE may provide unique insights regarding the neural mechanisms which underlie the development and progression of the disease. The measured mechanical property changes that we have observed warrant further exploration to investigate the diagnostic usefulness of MRE in cases of Alzheimer’s disease and other dementias.

Standard‐space atlas of the viscoelastic properties of the human brain

“…This work represents the first detailed investigation of the mechanical properties of parcellations of the cerebral cortex, though initial MRE investigations into cortical structure-function relationships Schwarb et al, 2019), contributions to adolescent risk-taking behavior (McIlvain et al, 2020), and the mechanical integrity of the cortex in Alzheimer's disease (Hiscox, Johnson, McGarry, Marshall, et al, 2020) This MRE study is the first to report significant sex differences in viscoelasticity in a wide range of neuroanatomical structures which supplements the wealth of existing data that reports sex differences in neuroanatomy. Interestingly, we found that female brains are approximately 4% more viscous compared to males as indicated by significantly higher ξ in global WM, which contradicts an early study that reported female brains were 9% less viscous in large regions primarily comprising white matter (Sack, Streitberger, Krefting, Paul, & Braun, 2011).…”

“… Note: Data from these studies have previously been published elsewhere, see Study A = Hiscox et al, 2018; Hiscox, Johnson, McGarry, Marshall, et al, 2020; Hiscox, Johnson, McGarry, Schwarb, et al, 2020; Study B = Schwarb, Johnson, McGarry, & Cohen, 2016; Schwarb et al, 2019, Johnson et al, 2016; Study C = Huesmann et al, 2020; Study D = Burzynska, Finc, Taylor, Knecht, & Kramer, 2017; Study E = Schwarb et al, 2017, Johnson et al, 2018. …”

“…We used a 19.6 mm cubic subzone, which has been standardized and maintained across all published brain MRE studies from our group. To further maintain consistency with our previously published work, maps of the complex shear modulus G* were reformulated to provide quantitative maps of shear stiffness, μ = 2jG * j 2 /(G 0 +jG * j), and damping ratio, Note: Data from these studies have previously been published elsewhere, see Study A = Hiscox et al, 2018;Hiscox, Johnson, McGarry, Marshall, et al, 2020;Hiscox, Johnson, McGarry, Schwarb, et al, 2020;Study B = Schwarb, Johnson, McGarry, & Cohen, 2016;Schwarb et al, 2019Study C = Huesmann et al, depending upon neuronal density and neurogenesis (Freimann et al, 2013;Klein et al, 2014), degree of myelination (Schregel et al, 2012; Weickenmeier et al, 2016; Weickenmeier, de Rooij, Budday, Ovaert, & Kuhl, 2017), and inflammation (Riek et al, 2012), and is the parameter most commonly reported to be affected in neurological disorders (Murphy et al, 2019). Damping ratio, ξ, is a F I G U R E 1 Overview of the MRE imaging and analysis procedure.…”

Mechanical alterations of the hippocampus in the APP/PS1 Alzheimer’s disease mouse model

“…The chronic neuroinflammation causes disease-related symptoms, such as loss of neurons and synapses ultimately leading to memory problems and dementia [13]. In addition to the underlying biological processes in AD, the investigation of mechanical properties received attention in recent years as a potential biomarker for early diagnosis, as shown by magnetic resonance elastography (MRE) studies where brain elasticity and viscosity decreased in AD human patients [14,15,16,17,18,19], and as a novel drug target for tissue regeneration [? 20].…”

The Other Side of Alzheimer’s Disease: Influence of Metabolic Disorder Features for Novel Diagnostic Biomarkers

“…Altogether, these findings suggest that in pathological conditions, adipokines promote Reactive Oxygen Species (ROS) overproduction and inflammatory processes, which are involved in BBB disruption and could potentially act on different brain regions such as the hippocampus ( Figure 4 ). This could explain why metabolic dysfunctions are associated with hippocampus atrophy and with an increased risk of developing dementia and AD [ 113 ]. In this regard, systemic alterations have been correlated to chronic inflammation caused by adiposity [ 114 , 115 , 116 ].…”