Theory of sleep/wake cycles affecting brain elastography

Abstract

As elastography of the brain finds increasing clinical applications, fundamental questions remain about baseline viscoelastic properties of the brain in 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 vs 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 wake/sleep 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.

Fluid compartments influence elastography of the aging mouse brain

“…If all the vessel radii are increased or decreased by a factor of where represents dilation and represents constriction, then we find where C is a constant based on material properties and the exponent of 1.5 is a plausible value derived from anatomical measures of the brain as explained in Ge et al ( 2022a ).…”

“…Thirty-five wild-type mice (C57BL/6, ranging from 2.5 to 30.6 months of age, 22 male/13 female, Charles River Laboratories, Wilmington, MA, USA) were scanned with 3D reverberant shear wave field optical coherence elastography (Rev3D-OCE) during anesthetized (mimicking sleep) states (Ge et al 2022a ). Cranial window surgeries were performed where 5 mm diameter glass windows replaced a portion of the skull near the center but leaning towards the right hemisphere (Mestre et al 2020 ).…”

“…In this section we summarize the main results from recent work on the biphasic (fluid/solid) microchannel flow model applied to the brain (Parker 2017 , Ge et al 2022a ). We derived the stress-strain behavior of the brain as a two-compartment model with a larger scale network representing the vascular and perivascular branching structures plus a smaller scale version representing the interstitial spaces, in particular the glymphatic system.…”

The expanding frontier of optical elastography and diagnostic biomechanics

“…As an example of high resolution elastography in living tissue, Figure 1 shows a study of elastography within a mouse brain, revealing the changes from awake to sleep states associated with diurnal changes in the glymphatic system. Reverberant shear wave activation was applied at 2000 Hz and internal shear wave propagation was scanned in 3D by an OCT system described in detail previously [12,13]. 1…”

“…4) Change with bio/cycles and treatments. As elastography becomes more widely available on clinical instruments, we can follow individuals as a function of time and as a function of treatments [13,19]. This creates the opportunity to study an individual's elastic properties as a function of important changes in conditions, and to assess the effectiveness of any treatments.…”