Aging brain mechanics: Progress and promise of magnetic resonance elastography

Abstract

Neuroimaging techniques that can sensitivity characterize healthy brain aging and detect subtle neuropathologies have enormous potential to assist in the early detection of neurodegenerative conditions such as Alzheimer's disease. Magnetic resonance elastography (MRE) has recently emerged as a reliable, high-resolution, and especially sensitive technique that can noninvasively characterize tissue biomechanical properties (i.e., viscoelasticity) in vivo in the living human brain. Brain tissue viscoelasticity provides a unique biophysical signature of neuroanatomy that are representative of the composition and organization of the complex tissue microstructure. In this article, we detail how progress in brain MRE technology has provided unique insights into healthy brain aging, neurodegeneration, and structure-function relationships. We further discuss additional promising technical innovations that will enhance the specificity and sensitivity for brain MRE to reveal considerably more about brain aging as well as its potentially valuable role as an imaging biomarker of neurodegeneration. MRE sensitivity may be particularly useful for assessing the efficacy of rehabilitation strategies, assisting in differentiating between dementia subtypes, and in understanding the causal mechanisms of disease which may lead to eventual pharmacotherapeutic development.

Keywords: Aging; Biomarkers; Brain; Mechanical properties; Neuroimaging; Stiffness.

Fig. 1.

Summary of the key events in brain aging MRE and the growth of brain MRE studies since the first publication in 2005. Manuscript production in absolute numbers per year. Search was performed in June 2020 using PubMed with key words “brain” and “magnetic resonance elastography” (Green et al., 2008, Curtis L Johnson et al., 2013, Kruse et al., 2008, McCracken et al., 2005).

Fig. 2.

Overview of a typical brain magnetic resonance elastography investigation. (a) An external pneumatic mechanical actuator is used to gently vibrate the head and generate steady-state shear wave fields in brain tissue; (b) specialized phase-contrast MRI sequences image the resulting displacements through synchronization with applied vibration; and (c) an inversion algorithm is used to recover mechanical properties from the imaged wave field: μ, shear stiffness (kPa), and ξ, damping ratio (dimensionless).

Fig. 3.

Structural T₁₋, weighted MRI images, and high-resolution MRE shear stiffness, μ, and damping ratio, ξ, maps for a (A) 23-year-old male, and (B) 65-year-old female. Widespread softer tissue and increased damping behavior is visibly notable in the older adult. Note that MRE inversion techniques do not model fluids and therefore are not valid in CSF spaces, including the lateral ventricles.

Fig. 4.

Summary of main findings that have used MRE to investigate brain stiffness in Alzheimer’s disease (AD). Color bar indicates percentage difference in AD patients compared to healthy controls (HC) in each of the respective studies. (A) Frontal (F), parietal (P), temporal (T) lobes, and a composite measure of deep gray/white matter (D) show AD-related softening, whereas the occipital lobe (O) remains unaffected; (B) analysis of subcortical structures indicate that the hippocampus (HP) is softer in AD, whereas the stiffness of the thalamus (TH) is relatively preserved; (C) cortical gray matter structures such as the superior temporal (ST), precentral (PCTL), precuneus (PCNS), and middle temporal (MT) cortex, show the greatest differences between AD and HC. These studies demonstrate the importance of obtaining high-resolution images for the investigation of ROIs with expected pathophysiology for greater sensitivity. Study A = Murphy et al., 2016; study B = Gerischer et al., 2018; study C = Hiscox et al., 2020a).

Fig. 5.

Results from three studies that have investigated the structure-function relationship between hippocampal viscoelasticity and memory score. In all studies, lower damping ratio was associated with better scores of memory performance, whereas hippocampal volume showed no relationship with performance in these tasks. Memory scores are from a spatial reconstruction task in studies 1 and 2 and from a verbal paired associates task in study 3. The blue line shows the regression line and the gray shaded region indicates the 95% confidence intervals. Study 1 = Schwarb et al., 2016; study 2 = Schwarb et al., 2017; study 3 = Hiscox et al., 2020b.