Dataset Information

Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys.

ABSTRACT: A detailed understanding of the CSF dynamics is needed for design and optimization of intrathecal drug delivery devices, drugs, and protocols. Preclinical research using large-animal models is important to help define drug pharmacokinetics-pharmacodynamics and safety. In this study, we investigated the impact of catheter implantation in the sub-dural space on CSF flow dynamics in Cynomolgus monkeys. Magnetic resonance imaging (MRI) was performed before and after catheter implantation to quantify the differences based on catheter placement location in the cervical compared to the lumbar spine. Several geometric and hydrodynamic parameters were calculated based on the 3D segmentation and flow analysis. Hagen-Poiseuille equation was used to investigate the impact of catheter implantation on flow reduction and hydraulic resistance. A linear mixed-effects model was used in this study to investigate if there was a statistically significant difference between cervical and lumbar implantation, or between two MRI time points. Results showed that geometric parameters did not change statistically across MRI measurement time points and did not depend on catheter location. However, catheter insertion did have a significant impact on the hydrodynamic parameters and the effect was greater with cervical implantation compared to lumbar implantation. CSF flow rate decreased up to 55% with the catheter located in the cervical region. The maximum flow rate reduction in the lumbar implantation group was 21%. Overall, lumbar catheter implantation disrupted CSF dynamics to a lesser degree than cervical catheter implantation and this effect remained up to two weeks post-catheter implantation in Cynomolgus monkeys.

SUBMITTER: Khani M

PROVIDER: S-EPMC7773283 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys.

Khani Mohammadreza M Fu Audrey Q AQ Pluid Joshua J Gibbs Christina P CP Oshinski John N JN Xing Tao T Stewart Gregory R GR Zeller Jillynne R JR Martin Bryn A BA

PloS one 20201230 12

A detailed understanding of the CSF dynamics is needed for design and optimization of intrathecal drug delivery devices, drugs, and protocols. Preclinical research using large-animal models is important to help define drug pharmacokinetics-pharmacodynamics and safety. In this study, we investigated the impact of catheter implantation in the sub-dural space on CSF flow dynamics in Cynomolgus monkeys. Magnetic resonance imaging (MRI) was performed before and after catheter implantation to quantify ...[more]

PMID: 33378399

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Project description:Untreated tricuspid valve regurgitation (TR) is associated with increased rates of mortality, morbidity, and hospitalization. Current pharmacological and surgical treatment options for TR are limited. MitraClip (MC), an edge-to-edge percutaneous intervention, has been reported to be effective for treatment of TR. The goal of this study was to examine the effects of MC position on TR, using a multiphysics fluid-structure-interaction (FSI) analysis. The computational set up included the tricuspid valve (TV), the chordae tendineae, the blood particles, and a tube that surrounded the leaflets and blood particles. The leaflets and chordae were modeled as hyperelastic materials, and blood was modeled using smoothed particle hydrodynamics. FSI analysis was conducted for blood flow through the closed valve for multiple simulations that account for normal, diseased, and treated conditions of the TV. To simulate the diseased TV, a group of chordae between septal and pulmonary leaflets were removed from the normal TV, which produced increased regurgitation. Four MC treated scenarios were considered: i) one MC near the annulus, ii) one MC approximately midway between the annulus and leaflet tip, iii) one MC near the leaflet tip, iv) two MCs: one approximately midway between the annulus and leaflet tip, and one close to the leaflet tip. The TR increased in diseased TV (7.5%) compared to normal TV (2.5%). All MC treated scenarios decreased TR. The MC located near the midway point between the annulus and leaflet tip led to largest decrease in TR (75.2% compared to the untreated condition). The MC located near the leaflet tip was associated with lowest reduction in TR (2.2% compared to the untreated condition). When two MCs were used, reduction in TR was relatively high (68.7%), but TR was not improved compared to the optimal single MC. MC caused high stresses in the vicinity of the clipping area in all conditions; the highest occurred when the MC was near the leaflet tips. Using a quantitative computational approach, we confirm previous clinical reports on the efficacy of MC for treatment of TR. The results of this study could lead to the design of more efficient MC interventions for TR.

Dataset Information

Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys.

Publications

Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys.

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