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

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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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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Cerebrospinal fluid drainage kinetics across the cribriform plate are reduced with aging

Fluids and Barriers of the CNS ◽

10.1186/s12987-020-00233-0 ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Molly Brady ◽

Akib Rahman ◽

Abigail Combs ◽

Chethana Venkatraman ◽

R. Tristan Kasper ◽

...

Keyword(s):

Spinal Cord ◽

Cerebrospinal Fluid ◽

Subarachnoid Space ◽

Ex Vivo ◽

Cribriform Plate ◽

Cervical Lymph Nodes ◽

Spinal Subarachnoid Space ◽

Ex Vivo Tissues ◽

The Brain

Abstract Background Continuous circulation and drainage of cerebrospinal fluid (CSF) are essential for the elimination of CSF-borne metabolic products and neuronal function. While multiple CSF drainage pathways have been identified, the significance of each to normal drainage and whether there are differential changes at CSF outflow regions in the aging brain are unclear. Methods Dynamic in vivo imaging of near infrared fluorescently-labeled albumin was used to simultaneously visualize the flow of CSF at outflow regions on the dorsal side (transcranial and -spinal) of the central nervous system. This was followed by kinetic analysis, which included the elimination rate constants for these regions. In addition, tracer distribution in ex vivo tissues were assessed, including the nasal/cribriform region, dorsal and ventral surfaces of the brain, spinal cord, cranial dura, skull base, optic and trigeminal nerves and cervical lymph nodes. Results Based on the in vivo data, there was evidence of CSF elimination, as determined by the rate of clearance, from the nasal route across the cribriform plate and spinal subarachnoid space, but not from the dorsal dural regions. Using ex vivo tissue samples, the presence of tracer was confirmed in the cribriform area and olfactory regions, around pial blood vessels, spinal subarachnoid space, spinal cord and cervical lymph nodes but not for the dorsal dura, skull base or the other cranial nerves. Also, ex vivo tissues showed retention of tracer along brain fissures and regions associated with cisterns on the brain surfaces, but not in the brain parenchyma. Aging reduced CSF elimination across the cribriform plate but not that from the spinal SAS nor retention on the brain surfaces. Conclusions Collectively, these data show that the main CSF outflow sites were the nasal region across the cribriform plate and from the spinal regions in mice. In young adult mice, the contribution of the nasal and cribriform route to outflow was much higher than from the spinal regions. In older mice, the contribution of the nasal route to CSF outflow was reduced significantly but not for the spinal routes. This kinetic approach may have significance in determining early changes in CSF drainage in neurological disorder, age-related cognitive decline and brain diseases.

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Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels

Journal of Experimental Medicine ◽

10.1084/jem.20190351 ◽

2019 ◽

Vol 216 (11) ◽

pp. 2492-2502 ◽

Cited By ~ 19

Author(s):

Qiaoli Ma ◽

Yann Decker ◽

Andreas Müller ◽

Benjamin V. Ineichen ◽

Steven T. Proulx

Keyword(s):

Cerebrospinal Fluid ◽

Subarachnoid Space ◽

Near Infrared ◽

Cranial Nerves ◽

Lymphatic Vessels ◽

Intraventricular Injection ◽

Spinal Subarachnoid Space ◽

Cord Injury ◽

Sacral Spine

The pathways of circulation and clearance of cerebrospinal fluid (CSF) in the spine have yet to be elucidated. We have recently shown with dynamic in vivo imaging that routes of outflow of CSF in mice occur along cranial nerves to extracranial lymphatic vessels. Here, we use near-infrared and magnetic resonance imaging to demonstrate the flow of CSF tracers within the spinal column and reveal the major spinal pathways for outflow to lymphatic vessels in mice. We found that after intraventricular injection, a spread of CSF tracers occurs within both the central canal and the spinal subarachnoid space toward the caudal end of the spine. Outflow of CSF tracers from the spinal subarachnoid space occurred predominantly from intravertebral regions of the sacral spine to lymphatic vessels, leading to sacral and iliac LNs. Clearance of CSF from the spine to lymphatic vessels may have significance for many conditions, including multiple sclerosis and spinal cord injury.

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Altered Cerebrospinal Fluid Clearance and Increased Intracranial Pressure in Rats 18 h After Experimental Cortical Ischaemia

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.712779 ◽

2021 ◽

Vol 14 ◽

Author(s):

Steven W. Bothwell ◽

Daniel Omileke ◽

Rebecca J. Hood ◽

Debbie-Gai Pepperall ◽

Sara Azarpeykan ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Intracranial Pressure ◽

Lymph Nodes ◽

Subarachnoid Space ◽

Ex Vivo ◽

Bimodal Distribution ◽

Cervical Lymph Nodes ◽

Post Stroke ◽

Spinal Subarachnoid Space

Oedema-independent intracranial pressure (ICP) rise peaks 20–22-h post-stroke in rats and may explain early neurological deterioration. Cerebrospinal fluid (CSF) volume changes may be involved. Cranial CSF clearance primarily occurs via the cervical lymphatics and movement into the spinal portion of the cranio-spinal compartment. We explored whether impaired CSF clearance at these sites could explain ICP rise after stroke. We recorded ICP at baseline and 18-h post-stroke, when we expect changes contributing to peak ICP to be present. CSF clearance was assessed in rats receiving photothrombotic stroke or sham surgery by intraventricular tracer infusion. Tracer concentration was quantified in the deep cervical lymph nodes ex vivo and tracer transit to the spinal subarachnoid space was imaged in vivo. ICP rose significantly from baseline to 18-h post-stroke in stroke vs. sham rats [median = 5 mmHg, interquartile range (IQR) = 0.1–9.43, n = 12, vs. −0.3 mmHg, IQR = −1.9–1.7, n = 10], p = 0.03. There was a bimodal distribution of rats with and without ICP rise. Tracer in the deep cervical lymph nodes was significantly lower in stroke with ICP rise (0 μg/mL, IQR = 0–0.11) and without ICP rise (0 μg/mL, IQR = 0–4.47) compared with sham rats (4.17 μg/mL, IQR = 0.74–8.51), p = 0.02. ICP rise was inversely correlated with faster CSF transit to the spinal subarachnoid space (R = −0.59, p = 0.006, Spearman’s correlation). These data suggest that reduced cranial clearance of CSF via cervical lymphatics may contribute to post-stroke ICP rise, partially compensated via increased spinal CSF outflow.

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Robot-assisted endoscopic exploration of the spinal cord

Proceedings of the Institution of Mechanical Engineers Part C Journal of Mechanical Engineering Science ◽

10.1243/09544062jmes2017 ◽

2010 ◽

Vol 224 (7) ◽

pp. 1515-1529 ◽

Cited By ~ 7

Author(s):

L Ascari ◽

C Stefanini ◽

U Bertocchi ◽

P Dario

Keyword(s):

Spinal Cord ◽

Subarachnoid Space ◽

Ex Vivo ◽

Hierarchical Control ◽

Three Dimensional ◽

Robot Assisted ◽

Actuation System ◽

Spinal Subarachnoid Space

This work presents the design and development of an integrated image-guided robot-assisted endoscopic system for the safe navigation within the spinal subarachnoid space, providing the surgeon with the direct vision of the structures (i.e. spinal cord, roots, vessels) and the possibility of performing some particularly useful operations, like local electrostimulation of nerve roots. The modelling, micro-fabrication, fluidic sustentation, and cable-based actuation system of a steerable tip for a multilumen flexible catheter is described; the hierarchical control system shared between the surgeon and the computer, and based on machine vision techniques and a simple but effective three-dimensional reconstruction is detailed. The Blind Expected Perception sensory-motor scheme is proposed in robot-assited endoscopy. Results from in vitro, ex vivo, and in vivo experiments show that the described model can accurately predict the shape of the catheter given the tension distribution on the cables, that the proposed actuation system can assure smooth and precise control of the catheter tip, that the fluidic sustentation of the catheter is essential in in vivo navigation, and that the proposed rear view mirror interface to show non-visible obstacles is appropriate; in conclusion, the results proved the validity of the proposed solution to develop an intrinsically safe robotic system for navigation and intervention in a narrow and challenging environment such as the spinal subarachnoid space.

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Noninvasive optical imaging of the subarachnoid space and cerebrospinal fluid pathways based on near-infrared fluorescence

Journal of Neurosurgery ◽

10.3171/jns.1997.87.5.0738 ◽

1997 ◽

Vol 87 (5) ◽

pp. 738-745 ◽

Cited By ~ 27

Author(s):

Kaoru Sakatani ◽

Masaki Kashiwasake-Jibu ◽

Yoshinori Taka ◽

Shijie Wang ◽

Huancong Zuo ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Injection Site ◽

Fluorescence Imaging ◽

Subarachnoid Space ◽

Near Infrared ◽

Content Type ◽

Spinal Subarachnoid Space ◽

Lumbar Spinal ◽

Fine Print

✓ The authors have developed a noninvasive optical method to image the subarachnoid space and cerebrospinal fluid pathways in vivo based on the near-infrared fluorescence of indocyanine green (ICG). The ICG was bound to purified lipoproteins (ICG—lipoprotein) and injected into the subarachnoid space of neonatal and adult rats. The ICG fluorescence was detected by a cooled charge-coupled device camera. After injection of ICG—lipoprotein into the cerebral subarachnoid space of the neonatal rat, ICG fluorescence was clearly detected at the injection site through the skull and skin. The ICG fluorescence was observed in the cerebellum and the lumbar spinal cord 1 and 8 hours postinjection, respectively. After injection of ICG—lipoprotein into the lumbar spinal subarachnoid space of an adult rat, ICG fluorescence was observed from the injection site to the thoracic levels along the spinal subarachnoid space. In addition, with the rat's head tilted downward, ICG fluorescence had extended to the cerebral subarachnoid space by 1 hour postinjection. The ICG fluorescence imaging of the cerebral subarachnoid space demonstrated an increase in fluorescence intensity around the lambdoid suture and the forebrain. On dissection of the rat brain the former location was identified as the supracerebellar cistern and the latter as the olfactory cistern. The results of this study are the first to demonstrate that an optical technique is applicable to imaging of the subarachnoid space and cerebrospinal fluid pathways in vivo. In addition, ICG—lipoprotein provides a sensitive optical tracer for imaging extravascular biological structures. Finally, ICG fluorescence imaging does not require an intricate imaging system because ICG is localized near the surface of the body.

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Pressure Wave Propagation in Fluid-Filled Co-Axial Elastic Tubes Part 2: Mechanisms for the Pathogenesis of Syringomyelia

Journal of Biomechanical Engineering ◽

10.1115/1.1634281 ◽

2003 ◽

Vol 125 (6) ◽

pp. 857-863 ◽

Cited By ~ 46

Author(s):

P. W. Carpenter ◽

K. Berkouk ◽

A. D. Lucey

Keyword(s):

Spinal Cord ◽

High Pressure ◽

Cerebrospinal Fluid ◽

Subarachnoid Space ◽

Leading Edge ◽

Propagation Mechanism ◽

Fluid System ◽

Elastic Tubes ◽

Spinal Subarachnoid Space ◽

Piston Mechanism

Our aim in this paper is to use a simple theoretical model of the intraspinal cerebrospinal-fluid system to investigate mechanisms proposed for the pathogenesis of syringomyelia. The model is based on an inviscid theory for the propagation of pressure waves in co-axial, fluid-filled, elastic tubes. According to this model, the leading edge of a pressure pulse tends to steepen and form an elastic jump, as it propagates up the intraspinal cerebrospinal-fluid system. We show that when an elastic jump is incident on a stenosis of the spinal subarachnoid space, it reflects to form a transient, localized region of high pressure within the spinal cord that for a cough-induced pulse is estimated to be 50 to 70 mm Hg or more above the normal level in the spinal subarachnoid space. We propose this as a new mechanism whereby pressure pulses created by coughing or sneezing can generate syrinxes. We also use the same analysis to investigate Williams’ suck mechanism. Our results do not support his concept, nor, in cases where the stenosis is severe, the differential-pressure-propagation mechanism recently proposed by Greitz et al. Our analysis does provide some support for the piston mechanism recently proposed by Oldfield et al. and Heiss et al. For instance, it shows clearly how the spinal cord is compressed by the formation of elastic jumps over part of the cardiac cycle. What appears to be absent for this piston mechanism is any means whereby the elastic jumps can be focused (e.g., by reflecting from a stenosis) to form a transient, localized region of high pressure within the spinal cord. Thus it would seem to offer a mechanism for syrinx progression, but not for its formation.

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