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Author
Date
2023Type
- Doctoral Thesis
ETH Bibliography
yes
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Abstract
Characterized by excessive buildup of fluid inside of the brain, Hydrocephalus stands as a major neurological concern, with hundreds of thousands of patients being diagnosed every year. Shunt-based treatment options, while seeing an innovative boom in the 20th century, have stagnated lately, leading to suboptimal operating procedure and treatment outcomes. Clinicians and patients call for better treatment solutions, be they shunt-based or not. More than 30% of all implanted shunts still fail within the first two years of implantation, necessitating revisions. Moreover, only 30% of all implanted shunts remain revision free within the first 10 years post-implantation. Of the shunts that do not require revision, they aim at simply saving the patient’s life by the diversion of cerebrospinal fluid (CSF) from the ventricles to prevent high intracranial pressures (ICP). They achieve this primarily by opening at a preselected or adjustable opening pressure. Consequently, they regulate the patient’s ICP to be stable at a certain level. Unfortunately, such a situation is far from physiological. Today it is known that the ICP in healthy individuals changes with activity, body position, arguably even with environmental air pressure. Yet, their relation to ICP remains unknown.
Herein provides the core aim of the thisthesis: to acquire a physiologic baseline of CSF and adjacent compartments such that a target for the reinstallation of “normal” physiology can be set, in turn allowing better evaluation of shunt-based therapeutic effectiveness.
To realize this aim, three studies were designed and conducted over the thesis’ course to develop a knowledge base on normal physiological values and relationships between the craniospinal, arteriovenous, and abdominal compartments in sheep given specific stimulations. The first study analyzed data from an acute anesthetized in-vivo trial and focused on the reactions and relationships between the intrathecal (ITP), ICP, carotid arterial blood (ABP), and central venous (CVP) pressures while ITP is artificially increased. It was observed that the pressure waveform propagated from ITP to ICP, then to ABP and CVP after the increase. Moreover, compensatory mechanisms in ABP were observed, believed to maintain proper cerebral perfusion pressure (CPP) given the acute increases in ICP. The results from Study I represent an important step into achieving a more complete quantitative understanding of how an acute rise in intrathecal pressure can propagate and influence other systems.
The second study, using the same raw dataset as was used in the analyses for the first study, investigated how ICP, ITP, carotid and femoral arterial (cABP, fABP), central and jugular venous (cABP, fABP), abdominal pressures in four directions, and bladder pressure all reacted and communicated during moderate head-up- and head-down-tilting. This augmented the physiologic knowledge base developed in the first study with seven new pressure sources and considering changes in body positions that directly influence all compartments. Tilt-tests with multicompartmental recordings help elucidate craniospinal, arterial, venous, and abdominal dynamics, which is essential to optimize shunt-based therapy. The results from Study II motivate hydrostatic influences on mean pressure, with all pressures correlating to posture, with little influence on pulse pressure. Transfer function (TF) results quantify the craniospinal, arterial, venous, and abdominal compartments as compliant systems and help pave the road for better quantitative models of the interaction between the craniospinal and adjacent spaces.
The third study focused on a dataset acquired during a chronic nonanesthetized, full awake ovine in-vivo trial comprised of six sheep. This analysis reported pressure dynamics between ICP, ITP, cABP, CVP, and abdominal compartments during a sheep chair – a 90˚ change in body position meant to simulate the change between prone and standing positions in humans. It was shown that there exists a compensatory reaction limiting the decrease of ICP that is not present in ITP following the positional change. Furthermore, that the abdominal compartment is incredibly heterogeneous and perhaps should not be considered as a homogeneous entity clinically. The results from Study III further augmented the physiologic knowledge base as developed from the previous two studies and provided a first-look into awake dynamics and their similarities/differences to an anesthetized state.
In conclusion, the studies conducted in this thesis contribute to an ever-evolving physiologic knowledge base with which therapeutic targets can be developed and new treatment methods can be tested and evaluated on. The relationships quantified during this thesis can specifically be used in the future development of intelligent shunt devices for a more effective treatment of hydrocephalus. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000660660Publication status
publishedExternal links
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Contributors
Examiner: Meboldt, Mirko
Examiner: Eklund, Anders
Examiner: Schmid Daners, Marianne
Examiner: Weisskopf, Miriam
Publisher
ETH ZurichOrganisational unit
03943 - Meboldt, Mirko / Meboldt, Mirko
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ETH Bibliography
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