Testing and Validation of Reciprocating Positive Displacement Pump for Benchtop Pulsating Flow Model of Cerebrospinal Fluid Production and Other Physiologic Systems

Background: The flow of physiologic fluids through organs and organs systems is an integral component of their function. The complex fluid dynamics in many organ systems are still not completely understood, and in-vivo measurements of flow rates and pressure provide a testament to the complexity of each flow system. Variability in in-vivo measurements and the lack of control over flow characteristics leave a lot to be desired for testing and evaluation of current modes of treatments as well as future innovations. In-vitro models are particularly ideal for studying neurological conditions such as hydrocephalus due to their complex pathophysiology and interactions with therapeutic measures. The following aims to present the reciprocating positive displacement pump, capable of inducing pulsating flow of a defined volume at a controlled beat rate and amplitude. While the other fluidic applications of the pump are currently under investigation, this study was focused on simulating the pulsating cerebrospinal fluid production across profiles with varying parameters. Methods: Pumps were manufactured using 3D printed and injection molded parts. The pumps were powered by an Arduino-based board and proprietary software that controls the linear motion of the pumps to achieve the specified output rate at the desired pulsation rate and amplitude. A range of 0.01 to 0.7 was tested to evaluate the versatility of the pumps. The accuracy and precision of the pumps’ output were evaluated by obtaining a total of 150 one-minute weight measurements of degassed deionized water per output rate across 15 pump channels. In addition, nine experiments were performed to evaluate the pumps’ control over pulsation rate and amplitude. Results: volumetric analysis of a total of 1200 readings determined that the pumps achieved the target output volume rate with a mean absolute error of -0.001034283 across the specified domain. It was also determined that the pumps can maintain pulsatile flow at a user-specified beat rate and amplitude. Conclusion: The validation of this reciprocating positive displacement pump system allows for the future validation of novel designs to components used to treat hydrocephalus and other physiologic models involving pulsatile flow. Based on the promising results of these experiments at simulating pulsatile CSF flow, a benchtop model of human CSF production and distribution could be achieved through the incorporation of a chamber system and a compliance component

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A coupled hydrodynamic model of the cardiovascular and cerebrospinal fluid system

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00658.2011 ◽

2012 ◽

Vol 302 (7) ◽

pp. H1492-H1509 ◽

Cited By ~ 32

Author(s):

Bryn A. Martin ◽

Philippe Reymond ◽

Jan Novy ◽

Olivier Balédent ◽

Nikolaos Stergiopulos

Keyword(s):

Blood Flow ◽

Cerebrospinal Fluid ◽

Cerebral Blood Flow ◽

Transfer Function ◽

Tube Model ◽

Tree Model ◽

Pulse Delay ◽

Arterial Network ◽

In Vivo Measurements

Coupling of the cardiovascular and cerebrospinal fluid (CSF) system is considered to be important to understand the pathophysiology of cerebrovascular and craniospinal disease and intrathecal drug delivery. A coupled cardiovascular and CSF system model was designed to examine the relation of spinal cord (SC) blood flow (SCBF) and CSF pulsations along the spinal subarachnoid space (SSS). A one-dimensional (1-D) cardiovascular tree model was constructed including a simplified SC arterial network. Connection between the cardiovascular and CSF system was accomplished by a transfer function based on in vivo measurements of CSF and cerebral blood flow. A 1-D tube model of the SSS was constructed based on in vivo measurements in the literature. Pressure and flow throughout the cardiovascular and CSF system were determined for different values of craniospinal compliance. SCBF results indicated that the cervical, thoracic, and lumbar SC each had a signature waveform shape. The cerebral blood flow to CSF transfer function reproduced an in vivo-like CSF flow waveform. The 1-D tube model of the SSS resulted in a distribution of CSF pressure and flow and a wave speed that were similar to those in vivo. The SCBF to CSF pulse delay was found to vary a great degree along the spine depending on craniospinal compliance and vascular anatomy. The properties and anatomy of the SC arterial network and SSS were found to have an important impact on pressure and flow and perivascular fluid movement to the SC. Overall, the coupled model provides predictions about the flow and pressure environment in the SC and SSS. More detailed measurements are needed to fully validate the model.

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Human CNS barrier-forming organoids with cerebrospinal fluid production

Science ◽

10.1126/science.aaz5626 ◽

2020 ◽

Vol 369 (6500) ◽

pp. eaaz5626 ◽

Cited By ~ 34

Author(s):

Laura Pellegrini ◽

Claudia Bonfio ◽

Jessica Chadwick ◽

Farida Begum ◽

Mark Skehel ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Fluid Secretion ◽

Fluid Production ◽

New Compounds ◽

High Degree ◽

The Brain ◽

Degree Of Similarity ◽

By Products

Cerebrospinal fluid (CSF) is a vital liquid, providing nutrients and signaling molecules and clearing out toxic by-products from the brain. The CSF is produced by the choroid plexus (ChP), a protective epithelial barrier that also prevents free entry of toxic molecules or drugs from the blood. Here, we establish human ChP organoids with a selective barrier and CSF-like fluid secretion in self-contained compartments. We show that this in vitro barrier exhibits the same selectivity to small molecules as the ChP in vivo and that ChP-CSF organoids can predict central nervous system (CNS) permeability of new compounds. The transcriptomic and proteomic signatures of ChP-CSF organoids reveal a high degree of similarity to the ChP in vivo. Finally, the intersection of single-cell transcriptomics and proteomic analysis uncovers key human CSF components produced by previously unidentified specialized epithelial subtypes.

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Bumetanide decreases canine cerebrospinal fluid production. In vivo evidence for NaCl cotransport in the central nervous system.

Journal of Clinical Investigation ◽

10.1172/jci116829 ◽

1993 ◽

Vol 92 (5) ◽

pp. 2257-2261 ◽

Cited By ~ 28

Author(s):

S Javaheri ◽

K R Wagner

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Fluid Production ◽

The Central Nervous System ◽

Nacl Cotransport

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A Coupled Simulation of Spinal Cord Blood Flow and Cerebrospinal Fluid Motion in the Spinal Subarachnoid Space Based on In Vivo Measurements

ASME 2011 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2011-53479 ◽

2011 ◽

Author(s):

Bryn Martin ◽

Philippe Reymond ◽

Olivier Balédent ◽

Jan Novy ◽

Nikos Stergiopulos

Keyword(s):

Spinal Cord ◽

Blood Flow ◽

Cerebrospinal Fluid ◽

Subarachnoid Space ◽

Tree Model ◽

Arterial Tree ◽

In Vivo Measurements ◽

Spinal Subarachnoid Space ◽

Systemic Arterial Tree

A preliminary coupled 1-D model of the systemic arterial tree and cerebrospinal fluid (CSF) system was constructed. The systemic tree model includes arteries greater than 2 mm in diameter and a simplified spinal cord vasculature. Coupling of the arterial tree and CSF system is accomplished by a transfer function based on in vivo cerebral blood flow (CBF) and CSF pulsation measurements in 17 young healthy adults. A 1-D tube model of the CSF in the spinal subarachnoid space (SSS) is formed based on in vivo measurements and used to determine flow and pressure along the SSS. The pressure and flow results in the CSF and systemic arterial tree are qualitatively and quantitatively similar to in vivo measurements in healthy subjects. The relative arrival time of blood pulsations in the spinal cord and CSF in the SSS is impacted by CSF system compliance and geometry. With low CSF system compliance the CSF pulsations arrive around the spinal cord before arterial pulsations and vice versa. Overall, the preliminary results support that geometric and mechanical properties of the CSF and cardiovascular system have an important impact on the flow and pressure environment and accent the importance to obtain in vivo measurements to improve modeling capabilities.

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Design, simulation and analysis of a positive displacement pump controller for biomedical applications requiring pulsatile flow

2017 IEEE Second Ecuador Technical Chapters Meeting (ETCM) ◽

10.1109/etcm.2017.8247491 ◽

2017 ◽

Author(s):

Hernan Lara-Padilla ◽

Ciro A. Rodriguez

Keyword(s):

Pulsatile Flow ◽

Biomedical Applications ◽

Positive Displacement ◽

Displacement Pump

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In Vivo Measurements of Cranial Electrical Stimulation Using Stereotactic-EEG: A Pilot Study

2021 10th International IEEE/EMBS Conference on Neural Engineering (NER) ◽

10.1109/ner49283.2021.9441106 ◽

2021 ◽

Author(s):

Minmin Wang ◽

Shenghua Zhu ◽

Haonan Guan ◽

Hongjie Jiang ◽

Jianmin Zhang ◽

...

Keyword(s):

Electrical Stimulation ◽

Pilot Study ◽

In Vivo Measurements

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Simulating a Ground Truth for Transit Time Analysis of Indicator Dilution Curves

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2020-3068 ◽

2020 ◽

Vol 6 (3) ◽

pp. 268-271

Author(s):

Michael Reiß ◽

Ady Naber ◽

Werner Nahm

Keyword(s):

Transit Time ◽

Sampling Rate ◽

Ground Truth ◽

Indicator Dilution ◽

Cross Sectional ◽

In Vivo Measurements ◽

Multiple Indicator Dilution ◽

Transit Times ◽

Dilution Curves

AbstractTransit times of a bolus through an organ can provide valuable information for researchers, technicians and clinicians. Therefore, an indicator is injected and the temporal propagation is monitored at two distinct locations. The transit time extracted from two indicator dilution curves can be used to calculate for example blood flow and thus provide the surgeon with important diagnostic information. However, the performance of methods to determine the transit time Δt cannot be assessed quantitatively due to the lack of a sufficient and trustworthy ground truth derived from in vivo measurements. Therefore, we propose a method to obtain an in silico generated dataset of differently subsampled indicator dilution curves with a ground truth of the transit time. This method allows variations on shape, sampling rate and noise while being accurate and easily configurable. COMSOL Multiphysics is used to simulate a laminar flow through a pipe containing blood analogue. The indicator is modelled as a rectangular function of concentration in a segment of the pipe. Afterwards, a flow is applied and the rectangular function will be diluted. Shape varying dilution curves are obtained by discrete-time measurement of the average dye concentration over different cross-sectional areas of the pipe. One dataset is obtained by duplicating one curve followed by subsampling, delaying and applying noise. Multiple indicator dilution curves were simulated, which are qualitatively matching in vivo measurements. The curves temporal resolution, delay and noise level can be chosen according to the requirements of the field of research. Various datasets, each containing two corresponding dilution curves with an existing ground truth transit time, are now available. With additional knowledge or assumptions regarding the detection-specific transfer function, realistic signal characteristics can be simulated. The accuracy of methods for the assessment of Δt can now be quantitatively compared and their sensitivity to noise evaluated.

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