Bulletin of the American Physical Society
75th Annual Meeting of the Division of Fluid Dynamics
Volume 67, Number 19
Sunday–Tuesday, November 20–22, 2022; Indiana Convention Center, Indianapolis, Indiana.
Session Q07: Cerebrospinal Fluid and Lymphatic Flow I |
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Chair: Javier Alaminos Quesada, University of California, San Diego Room: 134 |
Monday, November 21, 2022 1:25PM - 1:38PM |
Q07.00001: Fluid flow and transport of biotherapeutics through a 3D hybrid discrete-continuum vessel network in the skin tissue Dingding Han, Chenji Li, Soroush Araimdeh, Vivek Sree, Ehsan Rahimi, Adrian Buganza Tepole, Arezoo Ardekani Subcutaneous administration is a common approach for the delivery of biotherapeutics, which is achieved mainly through the absorption across lymphatic vessels. The drug transport and lymphatic uptake through a three-dimensional hybrid discrete-continuum vessel network in the skin tissue are investigated through high-fidelity numerical simulations. We find that the local lymphatic uptake through the explicit vessels significantly affects the macroscopic drug absorption. The diffusion of drug solute through the explicit vessel network affects the lymphatic uptake after the injection. This effect, however, cannot be captured using previously developed continuum models. Furthermore, the effects of injection volume and depth on the lymphatic uptake are investigated in a multi-layered domain. We find that the injection volume significantly affects the rate of the lymphatic uptake through the heterogeneous vessel network, while the injection depth has little influence. At last, the binding and metabolism of drug molecules are studied to bridge the simulation to the experimentally measured drug clearance. We provide a new approach to study the diffusion and convection of drug molecules into the lymphatic system through the hybrid vessel network. |
Monday, November 21, 2022 1:38PM - 1:51PM |
Q07.00002: Quantification of the rate of CSF clearance from PET scan images as a new computational marker for Alzheimer's Disease Priscilla Chang, Mony de Leon, Henry Rusinek, Yi Li, Xiuyuan Wang, Edward K Fung, Ke Xi, Mahdi Esmaily The current diagnostic techniques for Alzheimer's Disease rely on imaging the brain using CT, MRI, or PET. These techniques are typically subjective as they heavily rely on human judgment. This study attempts to introduce a more systematic approach that relies on the strong relationship between the rate of cerebrospinal fluid (CSF) clearance and the risk of Alzheimer's Disease. More specifically, this study investigates the possibility of extracting CSF flow rate from PET scan images by solving an inverse computational problem. The idea is to construct a model with unknown clearance rates as the model parameters, and then solve an optimization problem where those unknown parameters are tuned so that the model produces contrasts similar to those observed in the PET scan. In a blind study, we compare calculated CSF flow rates obtained from this process with the normal ranges for healthy patients to quantify the risk of Alzheimer's Disease. This new marker is then compared with the standard practice involving physicians' medical opinion that is directly based on the brain images. |
Monday, November 21, 2022 1:51PM - 2:04PM Author not Attending |
Q07.00003: Analysis of Cerebrospinal Fluid Rheology using Shear and Extensional Techniques John Hollister, Won Kim, Mayumi L Prins, Christopher C Giza, Pirouz Kavehpour Understanding the rheological behavior of cerebrospinal fluid (CSF) will be critical in the development of head-brain system biomechanical models as well as surgical and medical devices and techniques directed at alleviating intracranial pressure or altering CSF flow. CSF serves many functions in the head-brain system including cushioning the brain against impact, providing nutrient transport, and clearing waste via the glymphatic system. It is derived from blood plasma and is often considered a protein free Newtonian fluid, since typical CSF protein content is found to be between 25-60 mg/100g. However, it has been shown that the protein content of CSF can be different depending on the location (e.g. lumbar vs ventricular shunt) as well as condition of the patient (e.g. shunt infection, hemorrhage, or obstruction) from whom it has been extracted. In this study, we have performed a comprehensive rheological analysis of CSF specimens extracted from neurosurgical patients at the UCLA hospital. These specimens were tested using a conventional shear rheometer as well as a recently developed micro-extensional technique, which has been shown to be much more sensitive to protein content of dilute solutions. Preliminary tests show weak extensional behavior consistent with the protein concentration of CSF. The results of this study have shown that CSF exhibits quantifiable non-Newtonian behavior, and that this behavior may be influenced by the medical condition of the patient. Though the non-Newtonian contribution is relatively small, this characterization of CSF may have significant impacts on the development of brain models and medical technologies. |
Monday, November 21, 2022 2:04PM - 2:17PM |
Q07.00004: In-vitro experiments characterizing the cerebrospinal fluid flow in the central nervous system Obed A Campos, Francisco Moral-Pulido, Stephanie Sincomb, Carlos Martinez-Bazan, Antonio L Sanchez The characterization of cerebrospinal fluid (CSF) pulsatile-flow dynamics in the central nervous system (CNS) is fundamental for the study of CSF-related disorders. Recently developed theoretical descriptions for the CSF flow in the spinal canal and in the cerebral aqueduct can be used in combination with MRI flow-rate measurements to determine intracranial pressure temporal fluctuations and interventricular pressure differences. These descriptions have been validated via in-vitro experiments involving anatomically correct models. For the spinal canal, an elastic silicone model with relevant material properties reflective of the spinal-canal wave dynamics have been developed. Preliminary results indicate good agreement with the models. |
Monday, November 21, 2022 2:17PM - 2:30PM |
Q07.00005: Toward non-invasive intracranial pressure evaluation using a 1D model for the pulsating flow of cerebrospinal fluid in the spinal canal Stephanie Sincomb, Wilfried Coenen, Candido Gutiérrez-Montes, Carlos Martinez-Bazan, Victor Haughton, Antonio L Sanchez Continuous intracranial pressure (ICP) monitoring is key in the assessment of surgical intervention and guiding therapy for certain neurological diseases, but requires the insertion of pressure sensors, an invasive procedure with considerable risk factors. ICP fluctuations drive the wave-like pulsatile motion of cerebrospinal fluid (CSF) along the compliant spinal canal. A simple 1D model was developed for the pulsating viscous motion in the spinal canal assuming a linearly elastic compliant tube of slowly varying section, with a Darcy pressure-loss term included to model the fluid resistance introduced by the microanatomy. Use of Fourier-series expansions enables predictions of the CSF flow rate for realistic anharmonic ICP fluctuations. Here we explore the effect of the ICP signal morphology on the resulting flow rates to compare to measured flow rates from MRI. We also use the range of determined physiological parameters to perform the inverse problem using the flow rate to estimate the temporal variation of the ICP. |
Monday, November 21, 2022 2:30PM - 2:43PM |
Q07.00006: A new MRI-informed computational methodology for the characterization of drug dispersion in the spinal canal Guillermo Lopez Nozaleda, Javier Alaminos Quesada, Wilfried Coenen, Antonio L Sanchez Drug dispersion in intrathecal drug delivery processes, involving the injection of the drug into the cerebrospinal fluid (CSF) that fills the spinal canal, relies mainly on the slow Lagrangian drift stemming from the pulsatile motion induced by the cardiac and respiratory cycles. While MRI techniques can be successfully used to determine the spinal-canal anatomy and the pulsatile volumetric flow rate of CSF, they cannot describe with sufficient accuracy the slow Lagrangian drift, so that computational tools are needed to provide patient-specific predictions of drug dispersion. We present a new MRI-informed computational strategy that takes advantage of the slenderness of the canal and the existence of two different time scales, namely, the period of the CSF oscillatory motion and the much longer residence time associated with the Lagrangian drift. The development leads to a time-averaged, nonlinear integro-differential transport equation that describes the slow dispersion of the solute, thereby circumventing the need to describe the fast oscillatory motion. It is reasoned that the reduced-order description proposed here can provide accurate predictions of drug dispersion at a fraction of the computational cost associated with DNS computations. |
Monday, November 21, 2022 2:43PM - 2:56PM |
Q07.00007: The description of buoyancy effects on the dispersion of drugs released intrathecally in the spinal canal Javier Alaminos Quesada, Jenna J Lawrence, Candido Gutierrez-Montes, Wilfried Coenen, Antonio L Sanchez The transport of drugs along the spinal canal can be delivered by direct injection into the cerebrospinal fluid (CSF) that fills the intrathecal space surrounding the spinal cord. The analysis must account for the motion of the CSF, which moves under the action of the pressure oscillations induced by the cardiac and respiratory cycles. The resulting oscillatory velocity is known to have a time-averaged Lagrangian component, given by the sum of the steady-streaming and Stokes-drift velocities, which largely determines the drug dispersion rate along the canal. Attention is focused here on effects of buoyancy-induced motion. Although the relative density differences between the drug and the CSF are typically very small, on the order of 1/1000 for drugs diluted with water and 1/100 for drugs diluted with dextrose, the associated Richardson numbers are shown to be of order unity, so that the resulting buoyancy-induced velocities are comparable to those of steady streaming. Consequently, the slow time-averaged motion of the fluid particles is coupled with the transport of the drug, resulting in a slowly evolving steady-streaming problem that can be treated with two-time scale methods. The analysis produces a nonlinear transport equation that is used to illustrate effects of buoyancy in medical procedures involving drugs that are slightly denser or slightly lighter than the carrier fluid. |
Monday, November 21, 2022 2:56PM - 3:09PM |
Q07.00008: Floquet stability analysis of a two axisymmetric layers of oscillatory flow near a flexible wall as a model to study the flow induced in syringomyelia cavities Antonio J Barcenas-Luque, Carlos Martinez-Bazan, Candido Gutierrez-Montes, Antonio L Sanchez, Wilfried Coenen Syringomyelia is a disorder characterized by the accumulation of fluid in the spinal cord, forming macroscopic fluid-filled cavities, called syrinxes, the growth of which can lead to progressive neurological damage. It is widely accepted that both the hydrodynamics of the cerebrospinal fluid in the spinal subarachnoid space and the motion of the fluid inside the syringomyelia cavities, play an important role in their formation and growth. In the present work we are concerned with the coupling between the motion in these two fluid layers, driven by the flexible nature of the spinal-cord nervous tissue that separates them, and with their stability dynamics. In particular, we have studied a model problem involving the Floquet stability analysis of the oscillatory flow of two axisymmetric layers of fluid separated by an initially undeformed flexible wall, that is modelled as spring-backed plate. We have carried out an analysis for a wide range of flow and wall parameters, whose results show that, for different levels of coupling between the difference of forces (pressure and tangential stresses) across the wall and the wall deformation, a critical value of the Reynolds number exists above which the flow becomes unstable to perturbations. |
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