Theory of sleep/wake cycles affecting brain elastography

As elastography of the brain finds increasing clinical applications, fundamental questions remain about baseline viscoelastic properties of the brainin vivo. Furthermore, the underlying mechanisms of how and why elastographic measures can change over time are still not well understood. To study these issues, reverberant shear wave elastography using an optical coherence tomography scanner is implemented on a mouse model, both under awake conditions and in a sleep state where there are known changes in the glymphatic fluid flow system in the brain. We find that shear wave speed, a measure of stiffness, changes by approximately 12% between the two states, sleep versus awake, in the entire cortical brain imaging volume. Our microchannel flow model of biphasic (fluid plus solid) tissue provides a plausible rheological model based on the fractal branching vascular and perivascular system, plus a second parallel system representing the finer scale glymphatic fluid microchannels. By adjusting the glymphatic system fluid volume proportional to the known sleep/wake changes, we are able to approximately predict the measured shear wave speeds and their change with the state of the glymphatic system. The advantages of this model are that its main parameters are derived from anatomical measures and are linked to other major derivations of branching fluid structures including Murray's Law. The implications for clinical studies are that elastography of the brain is strongly influenced by the regulation or dysregulation of the vascular, perivascular, and glymphatic systems.