Numeriske simuleringer av adveksjons-dominert skalar-blanding anvendt på CSF-strømning og medikamenttransport

Studiet undersøker muligheten for å bruke Steamline Upwind/Petrov Galerkin (SUPG) og Discontinuous Galerkin (DG) i adveksjons-dominert skalar-blanding med høyt Schmidt-tall. Forenklede tester viste at DUPG og DG gir dårlig nøyaktighet dårlige egenskaper ved sjokk i løsningen. Uten sjokk i løsningen gav metodene god nøyaktighet. En pasient-spesifikk 3D-modell av den cervikale delen av Subaraknoidalrommet i en frisk person. To geometrier ble brukt; en uten mikro-anatomi, og en med idealiserte nerverøtter og denticulate ligamenter (NRDL) basert på in vivo-målinger fra litteraturen. CFD-simuleringer ble gjort med og uten NRDL for å finne innvirkningen til NRDL. Høyere hastigheter, større trykkgradient og et mer komplekst hastighetsfelt ble sett med NRDL. Sammenligning av strømlinjer med og uten NRDL viste virveldannelse i strømingsfeltet forårsaket av av NRDL. Inkluderingen av NRDL hadde liten innvirkning på fase-forsinkelsen mellom hastigheten og trykket. Etter 40 hjertesykluser ble det sett en 2.7 ganer så høy vertikal utstrekning av medikamentet med NRDL i forhold til uten NRDL, men konsentrasjonen ble 3 ganger så høy uten NRDL. Sensitivitetsanalyse av posisjon, elevasjon, asimiut, og injeksjonshastighet ble gjort. Innvirkningen på injeksjonshastighet og asimut-vinkel var liten, mens posisjon og elevasjonsvinkel gav signifikante endringer etter 13 hjertesykluser

A numerical investigation of intrathecal isobaric drug dispersion within the cervical subarachnoid space

Intrathecal drug and gene vector delivery is a procedure to release a solute within the cerebrospinal fluid. This procedure is currently used in clinical practice and shows promise for treatment of several central nervous system pathologies. However, intrathecal delivery protocols and systems are not yet optimized. The aim of this study was to investigate the effects of injection parameters on solute distribution within the cervical subarachnoid space using a numerical platform. We developed a numerical model based on a patient-specific three dimensional geometry of the cervical subarachnoid space with idealized dorsal and ventral nerve roots and denticulate ligament anatomy. We considered the drug as massless particles within the flow field and with similar properties as the CSF, and we analyzed the effects of anatomy, catheter position, angle and injection flow rate on solute distribution within the cerebrospinal fluid by performing a series of numerical simulations. Results were compared quantitatively in terms of drug peak concentration, spread, accumulation rate and appearance instant over 15 seconds following the injection. Results indicated that solute distribution within the cervical spine was altered by all parameters investigated within the time range analyzed following the injection. The presence of spinal cord nerve roots and denticulate ligaments increased drug spread by 60% compared to simulations without these anatomical features. Catheter position and angle were both found to alter spread rate up to 86%, and catheter flow rate altered drug peak concentration up to 78%. The presented numerical platform fills a first gap towards the realization of a tool to parametrically assess and optimize intrathecal drug and gene vector delivery protocols and systems. Further investigation is needed to analyze drug spread over a longer clinically relevant time frame

Drug accumulation rate (1/s) and appearance instant (s), as obtained by varying the injection speed.

<p>Drug accumulation rate (1/s) and appearance instant (s), as obtained by varying the injection speed.</p

Hydrodynamics parameters within each spinal segment resulting from test cases PS₁ and .

<p>Hydrodynamics parameters within each spinal segment resulting from test cases PS₁ and .</p

Cross-sectional views of the CSF velocity magnitude and dimensional drug concentration.

<p>(left) Magnitude of the CSF velocity at <i>t</i> = 20 <i>T</i> and (right) corresponding dimensional drug concentration (number of particles per volume) at Δ<i>y</i> = 0 <i>cm</i> (C5-level) for test cases S₄, S₅ and S₆.</p

Time evolution of the normalized drug concentration and relative linear fitting.

<p>The blue lines represent the time evolution of the normalized drug concentration at different cross sections from the injection point for (a) and (b) S₁. The red line indicates the relative linear fitting ().</p

Drug accumulation rate (1/s) and appearance instant (s), as obtained by varying the catheter position.

<p>Drug accumulation rate (1/s) and appearance instant (s), as obtained by varying the catheter position.</p

Normalized drug concentration profiles as a function of the distance Δ<i>y</i> from the injection point P₂ for different injection speeds.

<p>The profiles are obtained with test cases S₂, S₁₁, S₁₂.</p

Normalized drug concentration profiles as a function of the distance Δ<i>y</i> from the injection point for different injection positions.

<p>The profiles are obtained with test cases S₁-S₆.</p

Drug accumulation rate (1/s) and appearance instant (s), as obtained by varying the catheter angle.

<p>Drug accumulation rate (1/s) and appearance instant (s), as obtained by varying the catheter angle.</p