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      In vitro and numerical simulation of blood removal from cerebrospinal fluid: comparison of lumbar drain to Neurapheresis therapy

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          Abstract

          Background

          Blood removal from cerebrospinal fluid (CSF) in post-subarachnoid hemorrhage patients may reduce the risk of related secondary brain injury. We formulated a computational fluid dynamics (CFD) model to investigate the impact of a dual-lumen catheter-based CSF filtration system, called Neurapheresis™ therapy, on blood removal from CSF compared to lumbar drain.

          Methods

          A subject-specific multiphase CFD model of CSF system-wide solute transport was constructed based on MRI measurements. The Neurapheresis catheter geometry was added to the model within the spinal subarachnoid space (SAS). Neurapheresis flow aspiration and return rate was 2.0 and 1.8 mL/min, versus 0.2 mL/min drainage for lumbar drain. Blood was modeled as a bulk fluid phase within CSF with a 10% initial tracer concentration and identical viscosity and density as CSF. Subject-specific oscillatory CSF flow was applied at the model inlet. The dura and spinal cord geometry were considered to be stationary. Spatial–temporal tracer concentration was quantified based on time-average steady-streaming velocities throughout the domain under Neurapheresis therapy and lumbar drain. To help verify CFD results, an optically clear in vitro CSF model was constructed with fluorescein used as a blood surrogate. Quantitative comparison of numerical and in vitro results was performed by linear regression of spatial–temporal tracer concentration over 24-h.

          Results

          After 24-h, tracer concentration was reduced to 4.9% under Neurapheresis therapy compared to 6.5% under lumbar drain. Tracer clearance was most rapid between the catheter aspiration and return ports. Neurapheresis therapy was found to have a greater impact on steady-streaming compared to lumbar drain. Steady-streaming in the cranial SAS was ~ 50× smaller than in the spinal SAS for both cases. CFD results were strongly correlated with the in vitro spatial–temporal tracer concentration under Neurapheresis therapy (R 2 = 0.89 with + 2.13% and − 1.93% tracer concentration confidence interval).

          Conclusion

          A subject-specific CFD model of CSF system-wide solute transport was used to investigate the impact of Neurapheresis therapy on tracer removal from CSF compared to lumbar drain over a 24-h period. Neurapheresis therapy was found to substantially increase tracer clearance compared to lumbar drain. The multiphase CFD results were verified by in vitro fluorescein tracer experiments.

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          Most cited references63

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          Normal brain development and aging: quantitative analysis at in vivo MR imaging in healthy volunteers.

          To quantitate neuroanatomic parameters in healthy volunteers and to compare the values with normative values from postmortem studies. Magnetic resonance (MR) images of 116 volunteers aged 19 months to 80 years were analyzed with semiautomated procedures validated by means of comparison with manual tracings. Volumes measured included intracranial space, whole brain, gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). Results were compared with values from previous postmortem studies. Whole brain and intracranial space grew by 25%-27% between early childhood (mean age, 26 months; age range, 19-33 months) and adolescence (mean age, 14 years; age range, 12-15 years); thereafter, whole-brain volume decreased such that volunteers (age range, 71-80 years) had volumes similar to those of young children. GM increased 13% from early to later (6-9 years) childhood. Thereafter, GM increased more slowly and reached a plateau in the 4th decade; it decreased by 13% in the oldest volunteers. The GM-WM ratio decreased exponentially from early childhood through the 4th decade; thereafter, it gradually declined. In vivo patterns of change in the intracranial space, whole brain, and GM-WM ratio agreed with published postmortem data. MR images accurately depict normal patterns of age-related change in intracranial space, whole brain, GM, WM, and CSF. These quantitative MR imaging data can be used in research studies and clinical settings for the detection of abnormalities in fundamental neuroanatomic parameters.
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            Inspiration is the major regulator of human CSF flow.

            The mechanisms behind CSF flow in humans are still not fully known. CSF circulates from its primary production sites at the choroid plexus through the brain ventricles to reach the outer surface of the brain in the subarachnoid spaces from where it drains into venous bloodstream and cervical lymphatics. According to a recent concept of brain fluid transport, established in rodents, CSF from the brain surface also enters the brain tissue along para-arterial routes and exits through paravenous spaces again into subarachnoid compartments. This unidirectional flow is mainly driven by arterial pulsation. To investigate how CSF flow is regulated in humans, we applied a novel real-time magnetic resonance imaging technique at high spatial (0.75 mm) and temporal (50 ms) resolution in healthy human subjects. We observed significant CSF flow exclusively with inspiration. In particular, during forced breathing, high CSF flow was elicited during every inspiration, whereas breath holding suppressed it. Only a minor flow component could be ascribed to cardiac pulsation. The present results unambiguously identify inspiration as the most important driving force for CSF flow in humans. Inspiratory thoracic pressure reduction is expected to directly modulate the hydrostatic pressure conditions for the low-resistance paravenous, venous, and lymphatic clearance routes of CSF. Furthermore, the experimental approach opens new clinical opportunities to study the pathophysiology of various forms of hydrocephalus and to design therapeutic strategies in relation to CSF flow alterations.
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              Regulation of cerebrospinal fluid (CSF) flow in neurodegenerative, neurovascular and neuroinflammatory disease.

              Cerebrospinal fluid (CSF) circulation and turnover provides a sink for the elimination of solutes from the brain interstitium, serving an important homeostatic role for the function of the central nervous system. Disruption of normal CSF circulation and turnover is believed to contribute to the development of many diseases, including neurodegenerative conditions such as Alzheimer's disease, ischemic and traumatic brain injury, and neuroinflammatory conditions such as multiple sclerosis. Recent insights into CSF biology suggesting that CSF and interstitial fluid exchange along a brain-wide network of perivascular spaces termed the 'glymphatic' system suggest that CSF circulation may interact intimately with glial and vascular function to regulate basic aspects of brain function. Dysfunction within this glial vascular network, which is a feature of the aging and injured brain, is a potentially critical link between brain injury, neuroinflammation and the development of chronic neurodegeneration. Ongoing research within this field may provide a powerful new framework for understanding the common links between neurodegenerative, neurovascular and neuroinflammatory disease, in addition to providing potentially novel therapeutic targets for these conditions. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger.
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                Author and article information

                Contributors
                brynm@uidaho.edu
                Journal
                Fluids Barriers CNS
                Fluids Barriers CNS
                Fluids and Barriers of the CNS
                BioMed Central (London )
                2045-8118
                16 March 2020
                16 March 2020
                2020
                : 17
                : 23
                Affiliations
                [1 ]GRID grid.266456.5, ISNI 0000 0001 2284 9900, Department of Biological Engineering, , The University of Idaho, ; 875 Perimeter Drive, MS 0904, Moscow, ID 83844-0904 USA
                [2 ]GRID grid.266623.5, ISNI 0000 0001 2113 1622, Department of Mechanical Engineering, , University of Louisville, ; 332 Eastern Pkwy, Louisville, KY 40292 USA
                [3 ]Minnetronix Neuro, Inc., 1635 Energy Park Dr, Saint Paul, MN 55108 USA
                [4 ]GRID grid.26009.3d, ISNI 0000 0004 1936 7961, Department of Neurosurgery, , Duke University School of Medicine, ; 3100 Tower Blvd, Durham, NC 27707 USA
                Article
                185
                10.1186/s12987-020-00185-5
                7077023
                32178689
                d32d4a3b-6800-40de-932e-045f62bd2869
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 10 January 2020
                : 6 March 2020
                Funding
                Funded by: Minnetronix Corp
                Funded by: Institutional Development Award
                Award ID: P20GM1033408
                Award ID: 4U54GM104944-04TBD
                Award Recipient :
                Funded by: National Institute of Mental Health
                Award ID: 1R44MH112210-01A1
                Award Recipient :
                Funded by: University of Idaho Vandal Ideas Project
                Funded by: National Institute of Neurological Disorders and Stroke Grant
                Award ID: R01NS111283
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Neurology
                computational fluid dynamics,in-vitro model,subarachnoid hemorrhage,neurapheresis therapy,cerebrospinal fluid filtration,multiphase simulation

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