This paper investigates the transport of a solute carried by the cerebrospinal fluid (CSF) in the spinal canal. The analysis is motivated by the need for a better understanding of drug dispersion in connection with intrathecal drug delivery (ITDD), a medical procedure used for treatment of some cancers, infections and pain, involving the delivery of the drug to the central nervous system by direct injection into the CSF via the lumbar route. The description accounts for the CSF motion in the spinal canal, described in our recent publication (Sánchez et al., J. Fluid Mech., vol. 841, 2018, pp. 203–227). The Eulerian velocity field includes an oscillatory component with angular frequency $\unicode[STIX]{x1D714}$, equal to that of the cardiac cycle, and associated tidal volumes that are a factor $\unicode[STIX]{x1D700}\ll 1$ smaller than the total CSF volume in the spinal canal, with the small velocity corrections resulting from convective acceleration providing a steady-streaming component with characteristic residence times of order $\unicode[STIX]{x1D700}^{-2}\unicode[STIX]{x1D714}^{-1}\gg \unicode[STIX]{x1D714}^{-1}$. An asymptotic analysis for $\unicode[STIX]{x1D700}\ll 1$ accounting for the two time scales $\unicode[STIX]{x1D714}^{-1}$ and $\unicode[STIX]{x1D700}^{-2}\unicode[STIX]{x1D714}^{-1}$ is used to investigate the prevailing drug-dispersion mechanisms and their dependence on the solute diffusivity, measured by the Schmidt number $S$. Convective transport driven by the time-averaged Lagrangian velocity, obtained as the sum of the Eulerian steady-streaming velocity and the Stokes-drift velocity associated with the non-uniform pulsating flow, is found to be important for all values of $S$. By way of contrast, shear-enhanced Taylor dispersion, which is important for values of $S$ of order unity, is shown to be negligibly small for the large values $S\sim \unicode[STIX]{x1D700}^{-2}\gg 1$ corresponding to the molecular diffusivities of all ITDD drugs. Results for a model geometry indicate that a simplified equation derived in the intermediate limit $1\ll S\ll \unicode[STIX]{x1D700}^{-2}$ provides sufficient accuracy under most conditions, and therefore could constitute an attractive reduced model for future quantitative analyses of drug dispersion in the spinal canal. The results can be used to quantify dependences of the drug-dispersion rate on the frequency and amplitude of the pulsation of the intracranial pressure, the compliance and specific geometry of the spinal canal and the molecular diffusivity of the drug.
We present six cases of chondrodysplasia punctata with radiographic findings that are either very rare or previously unreported in this entity.
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.
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