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Understanding the physiological processes in aging and how neurodegenerative disorders affect cognitive function is a high priority for advancing human health. One specific area of recently enabled research is the in vivo biomechanical state of the brain. This study utilized reverberant optical coherence elastography, a high-resolution elasticity imaging method, to investigate stiffness changes during the sleep/wake cycle, aging, and Alzheimer's disease in murine models. Four-dimensional scans of 44 wildtype mice, 13 mice with deletion of aquaporin-4 water channel, and 12 mice with Alzheimer-related pathology (APP/PS1) demonstrated that (1) cortical tissue became softer (on the order of a 10% decrease in shear wave speed) when young wildtype mice transitioned from wake to anesthetized, yet this effect was lost in aging and with mice overexpressing amyloid-β or lacking the water channel AQP4. (2) Cortical stiffness increased with age in all mice lines, but wildtype mice exhibited the most prominent changes as a function of aging. The study provides novel insight into the brain's biomechanics, the constraints of fluid flow, and how the state of brain activity affects basic properties of cortical tissues., Competing Interests: Declaration of competing interest Authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective . Elastography of the brain has the potential to reveal subtle but clinically important changes in the structure and composition as a function of age, disease, and injury. Approach . In order to quantify the specific effects of aging on mouse brain elastography, and to determine the key factors influencing observed changes, we applied optical coherence tomography reverberant shear wave elastography at 2000 Hz to a group of wild-type healthy mice ranging from young to old age. Main results . We found a strong trend towards increasing stiffness with age, with an approximately 30% increase in shear wave speed from 2 months to 30 months within this sampled group. Furthermore, this appears to be strongly correlated with decreasing measures of whole brain fluid content, so older brains have less water and are stiffer. Rheological models are applied, and the strong effect is captured by specific assignment of changes to the glymphatic compartment of the brain fluid structures along with a correlated change in the parenchymal stiffness. Significance . Short-term and longer-term changes in elastography measures may provide a sensitive biomarker of progressive and fine-scale changes in the glymphatic fluid channels and parenchymal components of the brain., (Creative Commons Attribution license.)

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 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., (© 2022 Institute of Physics and Engineering in Medicine.)

Elastography researchers have utilized several rheological models to characterize soft tissue viscoelasticity over the past thirty years. Due to the frequency-dependent behavior of viscoelastic parameters as well as the different techniques and frequencies employed in various studies of soft tissues, rheological models have value in standardizing disparate techniques via explicit mathematical representations. However, the important question remains: which of the several available models should be considered for widespread adoption within a theoretical framework? We address this by evaluating the performance of three well established rheological models to characterize ex vivo bovine liver tissues: the Kelvin-Voigt (KV) model as a 2-parameter model, and the standard linear solid (SLS) and Kelvin-Voigt fractional derivative (KVFD) models as 3-parameter models. The assessments were based on the analysis of time domain behavior (using stress relaxation tests) and frequency domain behavior (by measuring shear wave speed (SWS) dispersion). SWS was measured over a wide range of frequency from 1 Hz to 1 kHz using three different tests: (i) harmonic shear tests using a rheometer, (ii) reverberant shear wave (RSW) ultrasound elastography scans, and (iii) RSW optical coherence elastography scans, with each test targeting a distinct frequency range. Our results demonstrated that the KVFD model produces the only mutually consistent rendering of time and frequency domain data for liver. Furthermore, it reduces to a 2-parameter model for liver (correspondingly to a 2-parameter "spring-pot" or power-law model for SWS dispersion) and provides the most accurate predictions of the material viscoelastic behavior in time (>98% accuracy) and frequency (>96% accuracy) domains. STATEMENT OF SIGNIFICANCE: Rheological models are applied in quantifying tissues viscoelastic properties. This study is unique in presenting comprehensive assessments of rheological models., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest with respect to this article., (Copyright © 2022. Published by Elsevier Ltd.)

Significance: Corneal cross-linking (CXL) is a well-known procedure for treating certain eye disorders such as keratoconus. However, characterization of the biomechanical changes in the cornea as a result of this procedure is still under active research. Specifically, there is a clinical need for high-resolution characterization of individual corneal layers., Aim: A high-resolution elastography method in conjunction with a custom optical coherence tomography system is used to track these biomechanical changes in individual corneal layers. Pre- and post-treatment analysis for both low-dose and high-dose CXL experiments are performed., Approach: A recently developed elastography technique that utilizes the theory of reverberant shear wave fields, with optical coherence tomography as the modality, is applied to pig corneas ex vivo to evaluate elasticity changes associated with corneal CXL. Sets of low-dose and high-dose CXL treatments are evaluated before and after treatments with three pairs of pig corneas per experiment., Results: The reverberant three-dimensional (3D) optical coherence elastography (OCE) technique can identify increases in elasticity associated with both low-dose and high-dose CXL treatments. There is a notable graphical difference between low-dose and high-dose treatments. In addition, the technique is able to identify which layers of the cornea are potentially affected by the CXL procedure and provides insight into the nonlinearity of the elasticity changes., Conclusions: The reverberant 3D OCE technique can identify depth-resolved changes in elasticity of the cornea associated with CXL procedures. This method could be translated to assess and monitor CXL efficacy in various clinical settings.