TY - JOUR
T1 - Exploring neurodegenerative disorders using a novel integrated model of cerebral transport
T2 - initial results
AU - Vardakis, John C.
AU - Chou, Dean
AU - Guo, Liwei
AU - Ventikos, Yiannis
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the European Commission FP7 project VPH-DARE@IT (FP7-ICT-2011-9-601055).
Funding Information:
We want to thank Dr A Sarrami-Foroushani, Dr N Ravikumar, Dr T Lassila, Mr Milton Hoz de Vila, Prof ZA Taylor and Prof AF Frangi from the University of Leeds for developing the models to generate subject-specific boundary conditions and meshes with permeability information, and the integrated workflows. We would like to thank Dr M Mitolo from Policlinico S. Orsola e Malpighi in Bologna and Prof A Venneri from the University of Sheffield for providing the clinical data for the subject-specific application. The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the European Commission FP7 project VPH-DARE@IT (FP7-ICT-2011-9-601055).
Publisher Copyright:
© IMechE 2020.
PY - 2020/10/20
Y1 - 2020/10/20
N2 - The neurovascular unit (NVU) underlines the complex and symbiotic relationship between brain cells and the cerebral vasculature, and dictates the need to consider both neurodegenerative and cerebrovascular diseases under the same mechanistic umbrella. Importantly, unlike peripheral organs, the brain was thought not to contain a dedicated lymphatics system. The glymphatic system concept (a portmanteau of glia and lymphatic) has further emphasized the importance of cerebrospinal fluid transport and emphasized its role as a mechanism for waste removal from the central nervous system. In this work, we outline a novel multiporoelastic solver which is embedded within a high precision, subject specific workflow that allows for the co-existence of a multitude of interconnected compartments with varying properties (multiple-network poroelastic theory, or MPET), that allow for the physiologically accurate representation of perfused brain tissue. This novel numerical template is based on a six-compartment MPET system (6-MPET) and is implemented through an in-house finite element code. The latter utilises the specificity of a high throughput imaging pipeline (which has been extended to incorporate the regional variation of mechanical properties) and blood flow variability model developed as part of the VPH-DARE@IT research platform. To exemplify the capability of this large-scale consolidated pipeline, a cognitively healthy subject is used to acquire novel, biomechanistically inspired biomarkers relating to primary and derivative variables of the 6-MPET system. These biomarkers are shown to capture the sophisticated nature of the NVU and the glymphatic system, paving the way for a potential route in deconvoluting the complexity associated with the likely interdependence of neurodegenerative and cerebrovascular diseases. The present study is the first, to the best of our knowledge, that casts and implements the 6-MPET equations in a 3D anatomically accurate brain geometry.
AB - The neurovascular unit (NVU) underlines the complex and symbiotic relationship between brain cells and the cerebral vasculature, and dictates the need to consider both neurodegenerative and cerebrovascular diseases under the same mechanistic umbrella. Importantly, unlike peripheral organs, the brain was thought not to contain a dedicated lymphatics system. The glymphatic system concept (a portmanteau of glia and lymphatic) has further emphasized the importance of cerebrospinal fluid transport and emphasized its role as a mechanism for waste removal from the central nervous system. In this work, we outline a novel multiporoelastic solver which is embedded within a high precision, subject specific workflow that allows for the co-existence of a multitude of interconnected compartments with varying properties (multiple-network poroelastic theory, or MPET), that allow for the physiologically accurate representation of perfused brain tissue. This novel numerical template is based on a six-compartment MPET system (6-MPET) and is implemented through an in-house finite element code. The latter utilises the specificity of a high throughput imaging pipeline (which has been extended to incorporate the regional variation of mechanical properties) and blood flow variability model developed as part of the VPH-DARE@IT research platform. To exemplify the capability of this large-scale consolidated pipeline, a cognitively healthy subject is used to acquire novel, biomechanistically inspired biomarkers relating to primary and derivative variables of the 6-MPET system. These biomarkers are shown to capture the sophisticated nature of the NVU and the glymphatic system, paving the way for a potential route in deconvoluting the complexity associated with the likely interdependence of neurodegenerative and cerebrovascular diseases. The present study is the first, to the best of our knowledge, that casts and implements the 6-MPET equations in a 3D anatomically accurate brain geometry.
KW - Alzheimer’s disease
KW - finite element method
KW - Glymphatic system
KW - multiple-network poroelastic theory
KW - neurovascular unit
UR - http://www.scopus.com/inward/record.url?scp=85093857517&partnerID=8YFLogxK
U2 - 10.1177/0954411920964630
DO - 10.1177/0954411920964630
M3 - Article
C2 - 33078663
AN - SCOPUS:85093857517
SN - 0954-4119
VL - 234
SP - 1223
EP - 1234
JO - Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine
JF - Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine
IS - 11
ER -