Patient Specific Hardware-in-the-Loop Testing of Cerebrospinal Fluid Shunt Systems

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BackgroundCerebrospinal fluid (CSF) protein analysis is an important element in the diagnostic chain for various central nervous system (CNS) pathologies. Among multiple existing approaches to interpreting measured protein levels, the Reiber diagram is particularly robust with respect to physiologic inter-individual variability, as it uses multiple subject-specific anchoring values. Beyond reliable identification of abnormal protein levels, the Reiber diagram has the potential to elucidate their pathophysiologic origin. In particular, both reduction of CSF drainage from the cranio-spinal space as well as blood–CNS barrier dysfunction have been suggested ρas possible causes of increased concentration of blood-derived proteins. However, there is disagreement on which of the two is the true cause.MethodsWe designed two computational models to investigate the mechanisms governing protein distribution in the spinal CSF. With a one-dimensional model, we evaluated the distribution of albumin and immunoglobulin G (IgG), accounting for protein transport rates across blood–CNS barriers, CSF dynamics (including both dispersion induced by CSF pulsations and advection by mean CSF flow) and CSF drainage. Dispersion coefficients were determined a priori by computing the axisymmetric three-dimensional CSF dynamics and solute transport in a representative segment of the spinal canal.ResultsOur models reproduce the empirically determined hyperbolic relation between albumin and IgG quotients. They indicate that variation in CSF drainage would yield a linear rather than the expected hyperbolic profile. In contrast, modelled barrier dysfunction reproduces the experimentally observed relation.ConclusionsHigh levels of albumin identified in the Reiber diagram are more likely to originate from a barrier dysfunction than from a reduction in CSF drainage. Our in silico experiments further support the hypothesis of decreasing spinal CSF drainage in rostro-caudal direction and emphasize the physiological importance of pulsation-driven dispersion for the transport of large molecules in the CSF.

Section: Discussionsupporting

confidence: 86%

Barrier dysfunction or drainage reduction: differentiating causes of CSF protein increase

Asgari

Zélicourt

Kurtcuoglu

2017

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“…Our results suggest a strong communication between ABP and cranio-spinal CSF pressure, reinforcing previous findings [ 22 ] and quantifying an important physiologic connection. Finally, the establishment of the sheep as a model to investigate CSF dynamics can help in the development a mechatronic platform for the further development and innovation of shunts [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Intercompartmental communication between the cerebrospinal and adjacent spaces during intrathecal infusions in an acute ovine in-vivo model

Podgoršak

Trimmel

Oertel

et al. 2022

Introduction The treatment of hydrocephalus has been a topic of intense research ever since the first clinically successful use of a valved cerebrospinal fluid shunt 72 years ago. While ample studies elucidating different phenomena impacting this treatment exist, there are still gaps to be filled. Specifically, how intracranial, intrathecal, arterial, and venous pressures react and communicate with each other simultaneously. Methods An in-vivo sheep trial (n = 6) was conducted to evaluate and quantify the communication existing within the cranio-spinal, arterial, and venous systems (1 kHz sampling frequency). Standardized intrathecal infusion testing was performed using an automated infusion apparatus, including bolus and constant pressure infusions. Bolus infusions entailed six lumbar intrathecal infusions of 2 mL Ringer’s solution. Constant pressure infusions were comprised of six regulated pressure steps of 3.75 mmHg for periods of 7 min each. Mean pressure reactions, pulse amplitude reactions, and outflow resistance were calculated. Results All sheep showed intracranial pressure reactions to acute increases of intrathecal pressure, with four of six sheep showing clear cranio-spinal communication. During bolus infusions, the increases of mean pressure for intrathecal, intracranial, arterial, and venous pressure were 16.6 ± 0.9, 15.4 ± 0.8, 3.9 ± 0.8, and 0.1 ± 0.2 mmHg with corresponding pulse amplitude increases of 2.4 ± 0.3, 1.3 ± 0.3, 1.3 ± 0.3, and 0.2 ± 0.1 mmHg, respectively. During constant pressure infusions, mean increases from baseline were 14.6 ± 3.8, 15.5 ± 4.2, 4.2 ± 8.2, and 3.2 ± 2.4 mmHg with the corresponding pulse amplitude increases of 2.5 ± 3.6, 2.5 ± 3.0, 7.7 ± 4.3, and 0.7 ± 2.0 mmHg for intrathecal, intracranial, arterial, and venous pulse amplitude, respectively. Outflow resistances were calculated as 51.6 ± 7.8 and 77.8 ± 14.5 mmHg/mL/min for the bolus and constant pressure infusion methods, respectively—showing deviations between the two estimation methods. Conclusions Standardized infusion tests with multi-compartmental pressure recordings in sheep have helped capture distinct reactions between the intrathecal, intracranial, arterial, and venous systems. Volumetric pressure changes in the intrathecal space have been shown to propagate to the intraventricular and arterial systems in our sample, and to the venous side in individual cases. These results 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.

“…1 . As most of the CSF system’s compensatory reserve is provided by concurrent venous volume adaptation, the CSF pressure–volume relationship was implemented as a function of the local CSF to venous pressure gradient [ 10 , 11 ]. This implies that an increase in CSF volume leads to a simultaneous displacement of venous blood from adjacent veins.…”

Section: Methodsmentioning

confidence: 99%

“…It is estimated in this study where the reference pressure is the sum of the postural pressure component and the venous pressure [ 11 , 14 ]. Describing the pressure–volume relation as a function of the CSF to venous pressure gradient, , allows changes in venous pressure to be accounted for [ 10 , 11 ]. In the model, the CSF space and the venous compartment were divided into a cranial and a spinal part.…”

Section: Methodsmentioning

confidence: 99%

Is posture-related craniospinal compliance shift caused by jugular vein collapse? A theoretical analysis

Gehlen

Kurtcuoglu

Daners

2017

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BackgroundPostural changes are related to changes in cerebrospinal fluid (CSF) dynamics. While sitting up leads to a decrease in cranial CSF pressure, it also causes shifts in the craniospinal CSF volume and compliance distribution. We hypothesized that jugular vein collapse in upright posture is a major contributor to these shifts in CSF volume and compliance.MethodsTo test this hypothesis, we implemented a mathematical lumped-parameter model of the CSF system and the relevant parts of the cardiovascular system. In this model, the CSF and the venous system are each divided into a cranial and a spinal part. The pressures in these cranial and spinal portions differ by the posture-dependent hydrostatic pressure columns in the connecting vessels. Jugular collapse is represented by a reduction of the hydrostatic pressure difference between cranial and spinal veins. The CSF pressure–volume relationship is implemented as a function of the local CSF to venous pressure gradient. This implies that an increase in CSF volume leads to a simultaneous displacement of blood from adjacent veins. CSF pulsations driven by the cardiovascular system are introduced through a pulsating cranial arterial volume.ResultsIn upright posture, the implemented CSF pressure–volume relationship shifts to lower cranial CSF pressures compared to the horizontal position, leading to a decrease in cranial CSF pressure when sitting up. Concurrently, the compliance of the spinal compartment decreases while the one of the cranial compartment increases. With this, in upright posture only 10% of the CSF system’s compliance is provided by the spinal compartment compared to 35% in horizontal posture. This reduction in spinal compliance is accompanied by a caudal shift of CSF volume. Also, the ability of the spinal CSF compartment to compensate for cerebral arterial volume pulsations reduces in upright posture, which in turn reduces the calculated craniospinal CSF flow pulsations.ConclusionThe mathematical model enabled us to isolate the effect of jugular collapse and quantify the induced shifts of compliance and CSF volume. The good concordance of the modelled changes with clinically observed values indicates that jugular collapse can be considered a major contributor to CSF dynamics in upright posture.