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Over the past decade, there has been a tremendously increased interest in understanding the neurophysiology of cerebrospinal fluid (CSF) flow, which plays a crucial role in clearing metabolic waste from the brain. This growing interest was largely initiated by two significant discoveries: the glymphatic system (a pathway for solute exchange between interstitial fluid deep within the brain and the CSF surrounding the brain) and meningeal lymphatic vessels (lymphatic vessels in the layer of tissue surrounding the brain that drains CSF). These two CSF systems work in unison, and their disruption has been implicated in several neurological disorders including Alzheimer's disease, stroke, and traumatic brain injury. Here, we present experimental techniques for in vivo quantification of CSF flow via direct imaging of fluorescent microspheres injected into the CSF. We discuss detailed image processing methods, including registration and masking of stagnant particles, to improve the quality of measurements. We provide guidance for quantifying CSF flow through particle tracking and offer tips for optimizing the process. Additionally, we describe techniques for measuring changes in arterial diameter, which is an hypothesized CSF pumping mechanism. Finally, we outline how these same techniques can be applied to cervical lymphatic vessels, which collect fluid downstream from meningeal lymphatic vessels. We anticipate that these fluid mechanical techniques will prove valuable for future quantitative studies aimed at understanding mechanisms of CSF transport and disruption, as well as for other complex biophysical systems. [ABSTRACT FROM AUTHOR]

Background: Flow of cerebrospinal fluid (CSF) through brain perivascular spaces (PVSs) is essential for the clearance of interstitial metabolic waste products whose accumulation and aggregation is a key mechanism of pathogenesis in many diseases. The PVS geometry has important implications for CSF flow as it affects CSF and solute transport rates. Thus, the size and shape of the perivascular spaces are essential parameters for models of CSF transport in the brain and require accurate quantification. Methods: We segmented two-photon images of pial (surface) PVSs and the adjacent arteries and characterized their sizes and shapes of cross sections from 14 PVS segments in 9 mice. Based on the analysis, we propose an idealized model that approximates the cross-sectional size and shape of pial PVSs, closely matching their area ratios and hydraulic resistances. Results: The ratio of PVS-to-vessel area varies widely across the cross sections analyzed. The hydraulic resistance per unit length of the PVS scales with the PVS cross-sectional area, and we found a power-law fit that predicts resistance as a function of the area. Three idealized geometric models were compared to PVSs imaged in vivo, and their accuracy in reproducing hydraulic resistances and PVS-to-vessel area ratios were evaluated. The area ratio was obtained across different cross sections, and we found that the distribution peaks for the original PVS and its closest idealized fit (polynomial fit) were 1.12 and 1.21, respectively. The peak of the hydraulic resistance distribution is 1.73 × 10 15 Pa s/m 5 and 1.44 × 10 15 Pa s/m 5 for the segmentation and its closest idealized fit, respectively. Conclusions: PVS hydraulic resistance can be reasonably predicted as a function of the PVS area. The proposed polynomial-based fit most closely captures the shape of the PVS with respect to area ratio and hydraulic resistance. Idealized PVS shapes are convenient for modeling, which can be used to better understand how anatomical variations affect clearance and drug transport. [ABSTRACT FROM AUTHOR]

The mixing of a reactive scalar by a fluid flow can have a significant impact on reaction dynamics and the growth of reacted regions. However, experimental studies of the fluid mechanics of reactive mixing present significant challenges and puzzling results. The observed speed at which reacted regions expand can be separated into a contribution from the underlying flow and a contribution from reaction–diffusion dynamics, which we call the chemical front speed. In prior work (Nevins & Kelley, Chaos, vol. 28 (4), 2018, 043122), we were surprised to observe that the chemical front speed increased where the underlying flow in a thin layer was faster. In this paper, we show that the increase is physical and is caused by smearing of reaction fronts by vertical shear. We show that the increase occurs not only in thin-layer flows with a free surface, but also in Hele-Shaw systems. We draw these conclusions from a series of simulations in which reaction fronts are located according to depth-averaged concentration, as is common in laboratory experiments. Where the front profile is deformed by shear, the apparent front speed changes as well. We compare the simulations to new experimental results and find close quantitative agreement. We also show that changes to the apparent front speed are reduced approximately 80 % by adding a lubrication layer. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) flowing through periarterial spaces is integral to the brain’s mechanism for clearing metabolic waste products. Experiments that track tracer particles injected into the cisterna magna (CM) of mouse brains have shown evidence of pulsatile CSF flow in perivascular spaces surrounding pial arteries, with a bulk flow in the same direction as blood flow. However, the driving mechanism remains elusive. Several studies have suggested that the bulk flow might be an artifact, driven by the injection itself. Here, we address this hypothesis with new in vivo experiments where tracer particles are injected into the CM using a dual-syringe system, with simultaneous injection and withdrawal of equal amounts of fluid. This method produces no net increase in CSF volume and no significant increase in intracranial pressure. Yet, particle-tracking reveals flows that are consistent in all respects with the flows observed in earlier experiments with single-syringe injection. [ABSTRACT FROM AUTHOR]