It is currently a well-established fact that the dynamics of interacting fluid compartments of the central nervous system (CNS) may play a role in the CNS fluid physiology and pathology of a number of neurological disorders, including neurodegenerative diseases associated with accumulation of waste products in the brain. However, the mechanisms and routes of waste clearance from the brain are still unclear. One of the main components of this interacting cerebral fluids dynamics is blood flow. In the last decades, mathematical modeling and fluid dynamics simulations have become a valuable complementary tool to experimental approaches, contributing to a deeper understanding of the circulatory physiology and pathology. However, modeling blood flow in the brain remains a challenging and demanding task, due to the high complexity of cerebral vascular networks and the difficulties that consequently arise to describe and reproduce the blood flow dynamics in these vascular districts. The first part of this work is devoted to the development of efficient numerical strategies for blood flow simulations in complex vascular networks. In cardiovascular modeling, one-dimensional (1D) and lumped-parameter (0D) models of blood flow are nowadays well-established tools to predict flow patterns, pressure wave propagation and average velocities in vascular networks, with a good balance between accuracy and computational cost. Still, the purely 1D modeling of blood flow in complex and large networks can result in computationally expensive simulations, posing the need for extremely efficient numerical methods and solvers. To address these issues, we develop a novel modeling and computational framework to construct hybrid networks of coupled 1D and 0D vessels and to perform computationally efficient and accurate blood flow simulations in such networks. Starting from a 1D model and a family of nonlinear 0D models for blood flow, with either elastic or viscoelastic tube laws, this methodology is based on (i) suitable coupling equations ensuring conservation principles; (ii) efficient numerical methods and numerical coupling strategies to solve 1D, 0D and hybrid junctions of vessels; (iii) model selection criteria to construct hybrid networks, which provide a good trade-off between accuracy in the predicted results and computational cost of the simulations. By applying the proposed hybrid network solver to very complex and large vascular networks, we show how this methodology becomes crucial to gain computational efficiency when solving networks and models where the heterogeneity of spatial and/or temporal scales is relevant, still ensuring a good level of accuracy in the predicted results. Hence, the proposed hybrid network methodology represents a first step towards a high-performance modeling and computational framework to solve highly complex networks of 1D-0D vessels, where the complexity does not only depend on the anatomical detail by which a network is described, but also on the level at which physiological mechanisms and mechanical characteristics of the cardiovascular system are modeled. Then, in the second part of the thesis, we focus on the modeling and simulation of cerebral blood flow, with emphasis on the venous side. We develop a methodology that, departing from the high-resolution MRI data obtained from a novel in-vivo microvascular imaging technique of the human brain, allows to reconstruct detailed subject-specific cerebral networks of specific vascular districts which are suitable to perform blood flow simulations.
First, we extract segmentations of cerebral districts of interest in a way that the arterio-venous separation is addressed and the continuity and connectivity of the vascular structures is ensured. Equipped with these segmentations, we propose an algorithm to extract a network of vessels suitable and good enough, i.e. with the necessary properties, to perform blood flow simulations. Here, we focus on the reconstruction of detailed venous vascular networks, given that the anatomy and patho-physiology of the venous circulation is of great interest from both clinical and modeling points of view. Then, after calibration and parametrization of the MRI-reconstructed venous networks, blood flow simulations are performed to validate the proposed methodology and assess the ability of such networks to predict physiologically reasonable results in the corresponding vascular territories. From the results obtained we conclude that this work represents a proof-of-concept study that demonstrates that it is possible to extract subject-specific cerebral networks from the novel high-resolution MRI data employed, setting the basis towards the definition of an effective processing pipeline for detailed blood flow simulations from subject-specific data, to explore and quantify cerebral blood flow dynamics, with focus on venous blood drainage.
| Identifer | oai:union.ndltd.org:unitn.it/oai:iris.unitn.it:11572/376527 |
| Date | 04 May 2023 |
| Creators | Ghitti, Beatrice |
| Contributors | Ghitti, Beatrice, Muller, Lucas Omar, Toro, Eleuterio Francisco |
| Publisher | Università degli studi di Trento, place:TRENTO |
| Source Sets | Università di Trento |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | firstpage:1, lastpage:226, numberofpages:226 |
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