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This paper investigates the transport of drugs delivered by direct injection into the cerebrospinal fluid (CSF) that fills the intrathecal space surrounding the spinal cord. Because of the small drug diffusivity, the dispersion of neutrally buoyant drugs has been shown in previous work to rely mainly on the mean Lagrangian flow associated with the CSF oscillatory motion. Attention is given here to effects of buoyancy, arising when the drug density differs from the CSF density. For the typical density differences found in applications, the associated Richardson number is shown to be of order unity, so that the Lagrangian drift includes a buoyancy-induced component that depends on the spatial distribution of the drug, resulting in a slowly evolving cycle-averaged flow problem that can be analysed with two-time scale methods. The asymptotic analysis leads to a nonlinear integro-differential equation for the spatiotemporal solute evolution that describes accurately drug dispersion at a fraction of the cost involved in direct numerical simulations of the oscillatory flow. The model equation is used to predict drug dispersion of positively and negatively buoyant drugs in an anatomically correct spinal canal, with separate attention given to drug delivery via bolus injection and constant infusion.

A simple two-dimensional fluid–structure interaction problem, involving viscous oscillatory flow in a channel separated by an elastic membrane from a fluid-filled slender cavity, is analysed to shed light on the flow dynamics pertaining to syringomyelia, a neurological disorder characterized by the appearance of a large tubular cavity (syrinx) within the spinal cord. The focus is on configurations in which the velocity induced in the cavity, representing the syrinx, is comparable to that found in the channel, representing the subarachnoid space surrounding the spinal cord, both flows being coupled through a linear elastic equation describing the membrane deformation. An asymptotic analysis for small stroke lengths leads to closed-form expressions for the leading-order oscillatory flow, and also for the stationary flow associated with the first-order corrections, the latter involving a steady distribution of transmembrane pressure. The magnitude of the induced flow is found to depend strongly on the frequency, with the result that for channel flow rates of non-sinusoidal waveform, as those found in the spinal canal, higher harmonics can dominate the sloshing motion in the cavity, in agreement with previous in vivo observations. Under some conditions, the cycle-averaged transmembrane pressure, also showing a marked dependence on the frequency, changes sign on increasing the cavity transverse dimension (i.e. orthogonal to the cord axis), underscoring the importance of cavity size in connection with the underlying hydrodynamics. The analytic results presented here can be instrumental in guiding future numerical investigations, needed to clarify the pathogenesis of syringomyelia cavities.

The classical problem of secondary flow driven by a sinusoidally varying pressure gradient is extended here to address periodic pressure gradients of complex waveform, which are present in many oscillatory physiological flows. A slender two-dimensional wavy-walled channel is selected as a canonical model problem. Following standard steady-streaming analyses, valid for small values of the ratio ε of the stroke length of the pulsatile motion to the channel wavelength, the spatially periodic flow is described in terms of power-law expansions of ε, with the Womersley number assumed to be of order unity. The solution found at leading order involves a time-periodic velocity with a zero time-averaged value at any given point. As in the case of a sinusoidal pressure gradient, effects of inertia enter at the following order to induce a steady flow in the form of recirculating vortices with zero net flow rate. An improved two-term asymptotic description of this secondary flow is sought by carrying the analysis to the following order. It is found that, when the pressure gradient has a waveform with multiple harmonics, the resulting velocity corrections display a nonzero flow rate, not present in the single-frequency case, which enables stationary convective transport along the channel. Direct numerical simulations for values of ε of order unity are used to investigate effects of inertia and delineate the range of validity of the asymptotic limit ε≪1. The comparisons of the time-averaged velocity obtained numerically with the two-term asymptotic description reveals that the latter remains remarkably accurate for values of ε exceeding 0.5. As an illustrative example, the results of the model problem are used to investigate the cerebrospinal-fluid flow driven along the spinal canal by the cardiac and respiratory cycles, characterized by markedly non-sinusoidal waveforms.

This paper presents results of an experimental investigation of solute transport in a simplified model of the spinal canal. The work aims to provide increased understanding of the mechanisms responsible for drug dispersion in intrathecal drug delivery (ITDD) procedures. The model consists of an annular channel bounded externally by a rigid transparent tube of circular section, representing the dura mater, and internally by an eccentric cylindrical compliant insert, representing the spinal cord. The tube, closed at one end, is connected to a rigid acrylic reservoir, representing the cranial cavity. The system is filled with water, whose properties are almost identical to those of the cerebrospinal fluid. A programmable peristaltic pump is employed to generate oscillatory motion at frequencies that are representative of those induced by the cardiac and respiratory cycles. Laser induced fluorescence is used to characterize the dispersion of fluorescent dye along the canal and into the cranial cavity for different values of the relevant Womersley number and different eccentricities of the annular section. The present work corroborates experimentally, for the first time, the existence of a steady bulk flow, associated with the mean Lagrangian motion, which plays a key role in the transport of the solute along the spinal canal. The measurements of solute dispersion are found to be in excellent agreement with theoretical predictions obtained using a simplified transport equation derived earlier on the basis of a two-timescale asymptotic analysis. The experimental results underscore the importance of the eccentricity and its variations along the canal and identifies changes in the flow topology associated with differences in the Womersley number, with potential implications in guiding future designs of ITDD protocols.

This paper addresses the viscous flow developing about an array of equally spaced identical circular cylinders aligned with an incompressible fluid stream whose velocity oscillates periodically in time. The focus of the analysis is on harmonically oscillating flows with stroke lengths that are comparable to or smaller than the cylinder radius, such that the flow remains two-dimensional, time-periodic and symmetric with respect to the centreline. Specific consideration is given to the limit of asymptotically small stroke lengths, in which the flow is harmonic at leading order, with the first-order corrections exhibiting a steady-streaming component, which is computed here along with the accompanying Stokes drift. As in the familiar case of oscillating flow over a single cylinder, for small stroke lengths, the associated time-averaged Lagrangian velocity field, given by the sum of the steady-streaming and Stokes-drift components, displays recirculating vortices, which are quantified for different values of the two relevant controlling parameters, namely, the Womersley number and the ratio of the inter-cylinder distance to the cylinder radius. Comparisons with results of direct numerical simulations indicate that the description of the Lagrangian mean flow for infinitesimally small values of the stroke length remains reasonably accurate even when the stroke length is comparable to the cylinder radius. The numerical integrations are also used to quantify the streamwise flow rate induced by the presence of the cylinder array in cases where the periodic surrounding motion is driven by an anharmonic pressure gradient, a problem of interest in connection with the oscillating flow of cerebrospinal fluid around the nerve roots located along the spinal canal.

This paper investigates flow and transport in a slender wavy-walled vertical channel subject to a prescribed oscillatory pressure difference between its ends. When the ratio of the stroke length of the pulsatile flow to the channel wavelength is small, the resulting flow velocity is known to include a slow steady-streaming component resulting from the effect of the convective acceleration. Our study considers the additional effect of gravitational forces in configurations with a non-uniform density distribution. Specific attention is given to the slowly evolving buoyancy-modulated flow emerging after the deposition of a finite amount of solute whose density is different from that of the fluid contained in the channel, a relevant problem in connection with drug dispersion in intrathecal drug delivery (ITDD) processes, involving the injection of the drug into the cerebrospinal fluid that fills the spinal canal. It is shown that when the Richardson number is of order unity, the relevant limit in ITDD applications, the resulting buoyancy-induced velocities are comparable to those of steady streaming. As a consequence, the slow time-averaged Lagrangian motion of the fluid, involving the sum of the Stokes drift and the time-averaged Eulerian velocity, is intimately coupled with the transport of the solute, resulting in a slowly evolving problem that can be treated with two-time-scale methods. The asymptotic 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 small concentration fluctuations associated with the fast oscillatory motion. The ideas presented here can find application in developing reduced models for future quantitative analyses of drug dispersion in the spinal canal.

Experiments have found substantial morphological differences between buoyancy-driven flames developing on the upper and lower surfaces of inclined burning plates. These differences cannot be explained on the basis of existing analytical solutions of steady semi-infinite flames, which provide identical descriptions for the top and bottom configurations. To investigate the potential role of flame instabilities in the experimentally observed flow differences, a temporal linear stability analysis is performed here. The problem is formulated in the limit of infinitely fast reaction, taking into account the non-unity Lewis number of the fuel vapor. The stability analysis incorporates non-parallel effects of the base flow and considers separately spanwise traveling waves and Görtler-like streamwise vortices. The solution to the stability eigenvalue problem determines the downstream location at which the flow becomes unstable, characterized by a critical value of the relevant Grashof number, whose value varies with the plate inclination angle. The results for the flame formed on the underside of the fuel surface indicate that instabilities emerge farther downstream than they do for a flame developing over the top of the fuel surface, in agreement with experimental observations. Increased buoyancy-induced vorticity production is reasoned to be responsible for the augmented instability tendency of topside flames.

This work is motivated by the interest in determining the effect of the micro-anatomy of the spinal subarachnoid space (SSAS) on the cerebrospinal fluid flow. To that aim, we model the nerve roots in the SSAS by circular posts of radius a, confined between two parallel plates separated by a distance 2h and subjected to an oscillatory flow of angular frequency ω. First, we analyze the asymptotic limit of small values of the dimensionless stroke length of the oscillatory flow, for a harmonic waveform, varying the aspect ratio of the post λ = h / a and the Womersley number W o = (a 2 ω / ν) 1 / 2 . For low values of Wo, the time-averaged steady flow exhibits symmetric recirculating vortices attached to the wall of the post whose size decreases as Wo increases. However, for values of Wo larger than a critical one, W o c (λ) , which depends on λ, a second, outer vortex is also formed. The dependence of W o c (λ) has been quantified in the range 0.5 < λ < ∞ , showing a decrease in Woc with λ. The analysis has been corroborated experimentally for λ = 2, and varying Wo, the stroke length as well as the wave form of the oscillating flow. Imposing an anharmonic oscillating flow shows that the fort-and-aft symmetry of the steady flow is broken, with the formation of two vortices of different size when W o < W o c and only one outer vortex in the systolic direction when W o > W o c . Finally, the study is experimentally extended considering an array of equally spaced posts, separated a semi-distance d = 2 a aligned with the flow. Qualitatively, the steady flow patterns induced for ℓ = d / a = 2 are similar to those for ℓ → ∞ , although the presence of the nearby posts confines the recirculating vortices and delays the flow transition, increasing W o c (λ). [ABSTRACT FROM AUTHOR]

This paper investigates the transport of drugs delivered by direct injection into the cerebrospinal fluid (CSF) that fills the intrathecal space surrounding the spinal cord. Because of the small drug diffusivity, the dispersion of neutrally buoyant drugs has been shown in previous work to rely mainly on the mean Lagrangian flow associated with the CSF oscillatory motion. Attention is given here to effects of buoyancy, arising when the drug density differs from the CSF density. For the typical density differences found in applications, the associated Richardson number is shown to be of order unity, so that the Lagrangian drift includes a buoyancy-induced component that depends on the spatial distribution of the drug, resulting in a slowly evolving cycle-averaged flow problem that can be analysed with two-time scale methods. The asymptotic analysis leads to a nonlinear integro-differential equation for the spatiotemporal solute evolution that describes accurately drug dispersion at a fraction of the cost involved in direct numerical simulations of the oscillatory flow. The model equation is used to predict drug dispersion of positively and negatively buoyant drugs in an anatomically correct spinal canal, with separate attention given to drug delivery via bolus injection and constant infusion. [ABSTRACT FROM AUTHOR]

This paper addresses the viscous flow developing about an array of equally spaced identical circular cylinders aligned with an incompressible fluid stream whose velocity oscillates periodically in time. The focus of the analysis is on harmonically oscillating flows with stroke lengths that are comparable to or smaller than the cylinder radius, such that the flow remains two-dimensional, time-periodic and symmetric with respect to the centreline. Specific consideration is given to the limit of asymptotically small stroke lengths, in which the flow is harmonic at leading order, with the first-order corrections exhibiting a steady-streaming component, which is computed here along with the accompanying Stokes drift. As in the familiar case of oscillating flow over a single cylinder, for small stroke lengths, the associated time-averaged Lagrangian velocity field, given by the sum of the steady-streaming and Stokes-drift components, displays recirculating vortices, which are quantified for different values of the two relevant controlling parameters, namely, the Womersley number and the ratio of the inter-cylinder distance to the cylinder radius. Comparisons with results of direct numerical simulations indicate that the description of the Lagrangian mean flow for infinitesimally small values of the stroke length remains reasonably accurate even when the stroke length is comparable to the cylinder radius. The numerical integrations are also used to quantify the streamwise flow rate induced by the presence of the cylinder array in cases where the periodic surrounding motion is driven by an anharmonic pressure gradient, a problem of interest in connection with the oscillating flow of cerebrospinal fluid around the nerve roots located along the spinal canal. [ABSTRACT FROM AUTHOR]

This paper investigates the air flow induced by a rigid circular disk or piston vibrating harmonically along its axis of symmetry in the immediate vicinity of a parallel surface. Previous attempts to characterize these so-called 'squeeze-film' systems largely relied on simplifications afforded by neglecting either fluid acceleration or viscous forces inside the thin enclosed gas layer. The present viscoacoustic analysis employs the asymptotic limit of small vibration amplitudes to investigate the flow by systematic reduction of the Navier-Stokes equations in two distinct flow regions, namely, the inner gaseous film where streamlines are nearly parallel to the confining walls and the near-edge region of non-slender flow that features gas exchange with the surrounding stagnant atmosphere. The flow in the gaseous film depends on the relevant Stokes number, defined as the ratio of the characteristic viscous time across the film to the characteristic oscillation time, and on a compressibility parameter, defined as the square of the ratio of the acoustic time for radial pressure equilibration to the oscillation time. A Strouhal number based on the local residence time emerges as an additional governing parameter for the near-edge region, which is incompressible at leading order. The method of matched asymptotic expansions is used to describe the solution in both regions, across which the time-averaged pressure exhibits comparable variations that give opposing contributions to the resulting time-averaged force experienced by the disk or piston. A diagram structured with the Stokes number and compressibility parameter as coordinates reveals that this steady squeeze-film force, typically repulsive for small values of the Stokes number, alternates to attraction across a critical separation contour in the parametric domain that exists for all Strouhal numbers. This analysis provides, for the first time, a unifying viscoacoustic theory of axisymmetric squeeze films, which yields a reduced parametric description for the time-averaged repulsion/attraction force that is potentially useful in applications including non-contact fluid bearings and robot locomotion. [ABSTRACT FROM AUTHOR]