The Networking Brain: How Extracellular Matrix, Cellular Networks, and Vasculature Shape the In Vivo Mechanical Properties of the Brain

Abstract Mechanically, the brain is characterized by both solid and fluid properties. The resulting unique material behavior fosters proliferation, differentiation, and repair of cellular and vascular networks, and optimally protects them from damaging shear forces. Magnetic resonance elastography (MRE) is a noninvasive imaging technique that maps the mechanical properties of the brain in vivo. MRE studies have shown that abnormal processes such as neuronal degeneration, demyelination, inflammation, and vascular leakage lead to tissue softening. In contrast, neuronal proliferation, cellular network formation, and higher vascular pressure result in brain stiffening. In addition, brain viscosity has been reported to change with normal blood perfusion variability and brain maturation as well as disease conditions such as tumor invasion. In this article, the contributions of the neuronal, glial, extracellular, and vascular networks are discussed to the coarse‐grained parameters determined by MRE. This reductionist multi‐network model of brain mechanics helps to explain many MRE observations in terms of microanatomical changes and suggests that cerebral viscoelasticity is a suitable imaging marker for brain disease.