Literature DB >> 29119834

Numerical study of intrathecal drug delivery to a permeable spinal cord: effect of catheter position and angle.

G Pizzichelli1, B Kehlet2, Ø Evju2, B A Martin3, M E Rognes2,4, K A Mardal2,4, E Sinibaldi1.   

Abstract

Intrathecal delivery is a procedure involving the release of therapeutic agents into the cerebrospinal fluid (CSF) hrough a catheter. It holds promise for treating high-impact central nervous system pathologies, for which systemic administration routes are ineffective. In this study we introduce a numerical model able to simultaneously account for solute transport in the fluid and in the spinal cord. Using a Discontinuous Galerkin method and a three-dimensional patient-specific geometry, we studied the effect of catheter position and angle on local spinal cord drug concentration. We considered twenty cardiac cycles to limit the computational cost of our approach, which resolves the physics both in space and time. We used clinically representative data for the drug injection speed and dose rate, and scaled drug diffusion/penetration properties to obtain observable effects during the considered simulation time. Based on our limited set of working parameters, lateral injection perpendicular to the cord turned out to be more effective than other configurations. Even if the adopted scaling does not allow for a direct clinical translation (a wider parametric assessment of the importance of CSF flow, geometry and diffusion properties is needed), it did not weaken our numerical approach, which can be used to systematically investigate multiple catheter, geometry and fluid/tissue properties configurations, thus paving the way for therapy control.

Entities:  

Keywords:  Discontinuous Galerkin method; Intrathecal drug delivery; cerebrospinal fluid; patient-specific numerical model; spinal cord; spinal subarachnoid space

Mesh:

Year:  2017        PMID: 29119834     DOI: 10.1080/10255842.2017.1393805

Source DB:  PubMed          Journal:  Comput Methods Biomech Biomed Engin        ISSN: 1025-5842            Impact factor:   1.763


  6 in total

1.  Anthropomorphic Model of Intrathecal Cerebrospinal Fluid Dynamics Within the Spinal Subarachnoid Space: Spinal Cord Nerve Roots Increase Steady-Streaming.

Authors:  Mohammadreza Khani; Lucas R Sass; Tao Xing; M Keith Sharp; Olivier Balédent; Bryn A Martin
Journal:  J Biomech Eng       Date:  2018-08-01       Impact factor: 2.097

2.  Characterization of intrathecal cerebrospinal fluid geometry and dynamics in cynomolgus monkeys (macaca fascicularis) by magnetic resonance imaging.

Authors:  Mohammadreza Khani; Braden J Lawrence; Lucas R Sass; Christina P Gibbs; Joshua J Pluid; John N Oshinski; Gregory R Stewart; Jillynne R Zeller; Bryn A Martin
Journal:  PLoS One       Date:  2019-02-27       Impact factor: 3.240

3.  In vitro and numerical simulation of blood removal from cerebrospinal fluid: comparison of lumbar drain to Neurapheresis therapy.

Authors:  Mohammadreza Khani; Lucas R Sass; M Keith Sharp; Aaron R McCabe; Laura M Zitella Verbick; Shivanand P Lad; Bryn A Martin
Journal:  Fluids Barriers CNS       Date:  2020-03-16

4.  Human in silico trials for parametric computational fluid dynamics investigation of cerebrospinal fluid drug delivery: impact of injection location, injection protocol, and physiology.

Authors:  Mohammadreza Khani; Goutham Kumar Reddy Burla; Lucas R Sass; Ostin N Arters; Tao Xing; Haiming Wu; Bryn A Martin
Journal:  Fluids Barriers CNS       Date:  2022-01-28

5.  Dispersion in porous media in oscillatory flow between flat plates: applications to intrathecal, periarterial and paraarterial solute transport in the central nervous system.

Authors:  M Keith Sharp; Roxana O Carare; Bryn A Martin
Journal:  Fluids Barriers CNS       Date:  2019-05-06

Review 6.  Translational Approaches for Brain Delivery of Biologics via Cerebrospinal Fluid.

Authors:  Shraddha S Sadekar; Mayumi Bowen; Hao Cai; Samira Jamalian; Hanine Rafidi; Whitney Shatz-Binder; Julien Lafrance-Vanasse; Pamela Chan; William J Meilandt; Amy Oldendorp; Alavattam Sreedhara; Ann Daugherty; Susan Crowell; Kristin R Wildsmith; Jasvinder Atwal; Reina N Fuji; Joshua Horvath
Journal:  Clin Pharmacol Ther       Date:  2022-02-23       Impact factor: 6.903

  6 in total

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