A Nonlinear Biphasic Model for Fluid Transport and Tissue Deformation During Constant Flow Rate Infusion Into Brain Tissue

2009 ◽  
Author(s):  
Joshua H. Smith ◽  
Jose Jaime García
Keyword(s):  
Brain Tissue ◽  
Fluid Transport ◽  
Solid Phase ◽  
Phase 1 ◽  
Therapeutic Agents ◽  
Tissue Deformation ◽  
Convection Enhanced Delivery ◽  
Adequate Treatment ◽  
Biphasic Model ◽  
Constant Flow Rate

The delivery of therapeutic agents into the brain is impeded by the blood-brain barrier, preventing adequate treatment of diseases of the central nervous system. Convection enhanced delivery was developed as a means to deliver therapeutic agents directly into brain tissue and to transport the drugs in the extracellular space using convective flow. Poroelastic or biphasic models have been used to study the concomitant fluid transport and tissue deformation that occurs during infusion, however previous studies have been limited by the assumption of linear elasticity of the solid phase [1].

A Nonlinear Biphasic Model for Mass Transport During Constant Flow-Rate Infusion Into Brain Tissue

2010 ◽  
Author(s):  
Joshua H. Smith ◽  
José Jaime García
Keyword(s):  
Mass Transport ◽  
Brain Tissue ◽  
Solid Phase ◽  
Phase 1 ◽  
Convection Enhanced Delivery ◽  
Biphasic Model ◽  
Constant Flow Rate ◽  
Nonlinear Stress ◽  
Tension And Compression ◽  
Rate Infusion

Convection-enhanced delivery is a means to deliver therapeutic agents directly into brain tissue. Biphasic models have been used to study the concomitant fluid and mass transport that occurs during infusion, however previous studies have been limited by the assumption of linear elasticity of the solid phase [1]. In contrast, nonlinear stress-strain curves have been documented for brain tissue under finite deformation in tension and compression [2, 3].

Effect of Transvascular Fluid Exchange for Nonlinear, Biphasic Analyses of Flow-Controlled Infusion in Brain

2011 ◽  
Author(s):  
Joshua H. Smith ◽  
Kathleen A. Starkweather ◽  
José Jaime García
Keyword(s):  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Therapeutic Agents ◽  
Constant Flow ◽  
Convection Enhanced Delivery ◽  
Fluid Exchange ◽  
Nonlinear Variation ◽  
Biphasic Model ◽  
Constant Flow Rate ◽  
Nonlinear Stress

Convection-enhanced delivery (CED) is a means to deliver therapeutic agents directly into brain tissue. Since CED often results in a rather significant interstitial fluid pressure, it is possible that infusions could result in a loss of fluid to the vasculature. While previous studies have included the effects of transvascular fluid exchange, they did so under the assumption of rigidity of the tissue [1, 2] or without considering its effect on the transport of the infused agent [3]. Recently, we proposed a spherical, biphasic model for constant flow-rate infusions that considers nonlinear stress-strain curves under finite deformation and nonlinear variation of hydraulic conductivity with deformation [4]. We have incorporated the effect of transvascular fluid exchange into this model and have studied the implications of variations in the vascular permeability, which may be of interest for improving drug delivery by CED.

A Biphasic Hyperelastic Model for Analysis of Fluid Transport in Brain Tissue

2008 ◽  
Author(s):  
Joshua H. Smith ◽  
Jose Jaime García
Keyword(s):  
Hydraulic Conductivity ◽  
Brain Tissue ◽  
Fluid Transport ◽  
Solid Phase ◽  
Finite Deformations ◽  
Positive Pressure ◽  
Convection Enhanced Delivery ◽  
Nonlinear Variation ◽  
Nonlinear Stress ◽  
Hyperelastic Model

Poroelastic or biphasic models have been used to study hydrocephalus [1] and the fluid transport that occurs during positive pressure infusion, also called convection enhanced delivery [2,3]. Each of the studies is limited by the assumption of linear elasticity of the solid phase. Nonlinear stress-strain curves under finite deformations have been documented for brain tissue under tension [4] and compression [5]. The nonlinear variation of hydraulic conductivity with strain has also recently been taken into account [1,3] and this effect has been deemed to play an important role in both the mechanics of the tissue and the associated fluid transport.

A Biphasic Viscoelastic Constitutive Model for Brain Tissue

2019 ◽  
Author(s):  
Mohammad Hosseini Farid ◽  
Mohammadreza Ramzanpour ◽  
Mariusz Ziejewski ◽  
Ghodrat Karami
Keyword(s):  
Constitutive Model ◽  
Brain Tissue ◽  
Mechanical Response ◽  
Solid Phase ◽  
Saturated Porous Medium ◽  
Bovine Brain ◽  
Coefficient Of Determination ◽  
Solid Matrix ◽  
Biphasic Model ◽  
Viscoelastic Constitutive Model

Abstract In this study, a rate-dependent biphasic model will be introduced to account for phenomenological behavior of brain tissue. For this purpose, a poro-hyper viscoelastic constitutive model is developed. The tissue is treated as a fluid-saturated porous medium, modeled as biphasic matter constituting of a solid matrix and interstitial liquids fill the porous spaces. The interactions between the two phases are assumed to be governed by Darcy’s law. This suggested model is calibrated with the experimental results of the bovine brain tissue, tested under high deformation rates (10, 100, 1000 mm/sec). The model will successfully take care of the detailed mechanical responses for solid and fluid phases, and their contributions to morphological behavior of this biological tissue. The material parameters of the model have been examined to agree well (R2 ≥ 0.96, where R is the coefficient of determination) with various deformation rates. In addition to representing the complete mechanical response and deformation of the solid phase, this biphasic model demonstrates the flow and diffusion of the liquid through the tissue networks.

A Strategy to Develop a Finite Element Model to Represent Backflow During Infusions Into Brain Tissue

2011 ◽  
Author(s):  
Ana Belly Molano ◽  
José Jaime García ◽  
Joshua H. Smith
Keyword(s):  
Central Nervous System ◽  
Finite Element ◽  
Clinical Trials ◽  
Nervous System ◽  
Brain Tissue ◽  
Element Model ◽  
Therapeutic Agents ◽  
Convection Enhanced Delivery ◽  
Limited Efficacy ◽  
The Central Nervous System

Convection-enhanced delivery is a means to deliver therapeutic agents directly into brain tissue for the treatment of brain tumors and other disorders of the central nervous system. Unfortunately, recent clinical trials have demonstrated limited efficacy of this procedure and suggested that one of the main obstacles is poor distribution of the infused agent [1].

Predictions of Drug Distribution During Infusions Into the Brain Using an Axisymmetric Finite Element Biphasic Model That Includes Backflow

2013 ◽  
Author(s):  
Alejandro Orozco ◽  
Joshua H. Smith ◽  
José Jaime García
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Drug Distribution ◽  
Therapeutic Agents ◽  
Positive Pressure ◽  
Convection Enhanced Delivery ◽  
Biphasic Model ◽  
Limited Efficacy ◽  
The Central Nervous System ◽  
The Brain

Convection-enhanced delivery is a technique to infuse therapeutic agents into the brain under positive pressure for the treatment of disorders of the central nervous system. Recent clinical trials [1] have shown limited efficacy of this procedure, attributed to poor distribution of the infused agent that may be due to backflow, in which the infused fluid preferentially flows along the outside of the catheter toward the surface of the brain.

scholarly journals DDRE-21. PNOC015: PHASE 1 STUDY OF MTX110 DELIVERED BY CONVECTION ENHANCED DELIVERY (CED) IN CHILDREN WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) PREVIOUSLY TREATED WITH RADIATION THERAPY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii66-ii66
Author(s):  
Sabine Mueller ◽  
Cassie Kline ◽  
Javier Villanueva-Meyer ◽  
Carly Hoffman ◽  
Shannon Raber ◽  
...  
Keyword(s):  
Phase 1 ◽  
Volume Ratio ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Newly Diagnosed ◽  
Convection Enhanced Delivery ◽  
Catheter Position ◽  
Pharmacodynamic Effects ◽  
Distribution Volume Ratio ◽  
Previously Treated ◽  
Grade 3

Abstract OBJECTIVE To determine safety and distribution of MTX110 delivered by CED in newly diagnosed DIPG patients. METHODS DIPG patients (3–21 years) were enrolled after radiation. CED of MTX110 combined with gadoteridol was completed based on dose levels (DL) (30–90 µM with volumes ranging from 3 cc (single dose) to 2 consecutive doses of 6 cc; total number of DL=7). Catheter position was chosen to maximize tumor coverage. Distribution of infusate was monitored with real-time MR imaging. Repeat CED was performed every 4–8 weeks if tolerated. Quality of life (QOL) assessments using PedsQL Generic Core and Brain Tumor modules were obtained at baseline (n=5), 3-months (n=3), and end of therapy (n=2). Single-cell RNA sequencing and analysis of histone modifications was performed to assess pharmacodynamic effects on DIPG cells. RESULTS Between May 2018-Dec 2019, 6 patients were enrolled (median age 8 years, range 5–21). Dose limiting toxicities included: grade 3 gait disturbance (DL7; cycle 1); grade 3 muscle weakness/vagus nerve disorder (DL5; cycle 4) and grade 2 intolerable dysphagia (DL7; cycle 4). Twelve CED procedures were completed at DL7 and repeated cycles ranged from 2 to 7. Infusion to distribution volume ratio was approximately 1:3.5. There were no significant changes in self-reported QOL. Parent ratings of patients’ worry (p = 0.04) and overall QOL (p = 0.03) significantly decreased at 3-months. CONCLUSION Repeat CED of MTX110 at the highest dose is tolerable. Tissue concentrations are likely to be substantially higher compared to oral dosing. Pharmacodynamic effects will be presented.

scholarly journals Strain Tensor Imaging: Cardiac-induced brain tissue deformation in humans quantified with high-field MRI

NeuroImage ◽  
2021 ◽  
pp. 118078
Author(s):  
Jacob-Jan Sloots ◽  
Geert Jan Biessels ◽  
Alberto de Luca ◽  
Jaco J.M. Zwanenburg
Keyword(s):  
Brain Tissue ◽  
High Field ◽  
Strain Tensor ◽  
Tissue Deformation ◽  
High Field Mri
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