Interstitial and cerebrospinal fluid exchanging process revealed by phase alternate labeling with null recovery MRI

Recovery Curves ◽

Ependymal Layer ◽

Apparent Diffusion ◽

The Difference ◽

Purpose: To develop Phase Alternate LAbeling with Null recovery (PALAN) MRI methods for the quantification of interstitial to cerebrospinal fluid flow (ICF) and cerebrospinal to interstitial fluid flow (CIF) in the brain. Method: In both T1-PALAN and apparent diffusion coefficient (ADC)-PALAN MRI methods, the cerebrospinal fluid (CSF) signal was nulled, while the residual interstitial fluid (ISF) was labeled by alternating the phase of pulses. ICF was extracted from the difference between the recovery curves of CSF with and without labeling. Similarly, CIF was measured by the T2-PALAN MRI method by labeling CSF, which took advance of the significant T2 difference between CSF and parenchyma. Results: Both T1-PALAN and ADC-PALAN observed a rapid occurrence of ICF at 67±56 ms and 13±2 ms interstitial fluid transit times, respectively. ICF signal peaked at 1.5 s for both methods. ICF was 1153±270 ml/100ml/min with T1-PALAN in the third and lateral ventricles, which was higher than 891±60 ml/100ml/min obtained by ADC-PALAN. The results of the T2-PALAN suggested the ISF exchanging from ependymal layer to the parenchyma was extremely slow. Conclusion: The PALAN methods are suitable tools to study ISF and CSF flow kinetics in the brain.

Spatially Organized Ciliary Beating Compartmentalizes Cerebrospinal Fluid Flow in the Brain and Regulates Ventricular Development

SSRN Electronic Journal ◽

10.2139/ssrn.3199994 ◽

2018 ◽

Cited By ~ 1

Author(s):

Emilie W. Olstad ◽

Christa Ringers ◽

Adinda Wens ◽

Jan N. Hansen ◽

Cecilia Brandt ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Fluid Flow ◽

Ciliary Beating ◽

Ciliary Beating Compartmentalizes Cerebrospinal Fluid Flow in the Brain and Regulates Ventricular Development

Current Biology ◽

10.1016/j.cub.2018.11.059 ◽

2019 ◽

Vol 29 (2) ◽

pp. 229-241.e6 ◽

Cited By ~ 45

Author(s):

Emilie W. Olstad ◽

Christa Ringers ◽

Jan N. Hansen ◽

Adinda Wens ◽

Cecilia Brandt ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Fluid Flow ◽

Ciliary Beating ◽

A novel hypomorphic allele of Spag17 causes primary ciliary dyskinesia phenotypes in mice

Disease Models & Mechanisms ◽

10.1242/dmm.045344 ◽

2020 ◽

Vol 13 (10) ◽

pp. dmm045344

Author(s):

Zakia Abdelhamed ◽

Marshall Lukacs ◽

Sandra Cindric ◽

Heymut Omran ◽

Rolf W. Stottmann

Keyword(s):

Cerebrospinal Fluid ◽

Fluid Flow ◽

Primary Ciliary Dyskinesia ◽

Human Condition ◽

Central Pair ◽

Hypomorphic Allele ◽

Motile Cilia ◽

The Brain ◽

Ciliary Dyskinesia

ABSTRACTPrimary ciliary dyskinesia (PCD) is a human condition of dysfunctional motile cilia characterized by recurrent lung infection, infertility, organ laterality defects and partially penetrant hydrocephalus. We recovered a mouse mutant from a forward genetic screen that developed many of the hallmark phenotypes of PCD. Whole-exome sequencing identified this primary ciliary dyskinesia only (Pcdo) allele to be a nonsense mutation (c.5236A>T) in the Spag17 coding sequence creating a premature stop codon (K1746*). The Pcdo variant abolished several isoforms of SPAG17 in the Pcdo mutant testis but not in the brain. Our data indicate differential requirements for SPAG17 in different types of motile cilia. SPAG17 is essential for proper development of the sperm flagellum and is required for either development or stability of the C1 microtubule structure within the central pair apparatus of the respiratory motile cilia, but not the brain ependymal cilia. We identified changes in ependymal ciliary beating frequency, but these did not appear to alter lateral ventricle cerebrospinal fluid flow. Aqueductal stenosis resulted in significantly slower and abnormally directed cerebrospinal fluid flow, and we suggest that this is the root cause of the hydrocephalus. The Spag17Pcdo homozygous mutant mice are generally viable to adulthood but have a significantly shortened lifespan, with chronic morbidity. Our data indicate that the c.5236A>T Pcdo variant is a hypomorphic allele of Spag17 that causes phenotypes related to motile, but not primary, cilia. Spag17Pcdo is a useful new model for elucidating the molecular mechanisms underlying central pair PCD pathogenesis in the mouse.This article has an associated First Person interview with the first author of the paper.

Apparent Diffusion Coefficient and Cerebrospinal Fluid Flow Measurements in Patients With Hydrocephalus

Journal of Computer Assisted Tomography ◽

10.1097/rct.0b013e31812f4edc ◽

2008 ◽

Vol 32 (3) ◽

pp. 392-396 ◽

Cited By ~ 15

Author(s):

Yonca Anik ◽

Ali Demirci ◽

Ihsan Anik ◽

Volkan Etus ◽

Arzu Arslan

Keyword(s):

Cerebrospinal Fluid ◽

Diffusion Coefficient ◽

Fluid Flow ◽

Apparent Diffusion Coefficient ◽

Flow Measurements ◽

Apparent Diffusion

Autologous Gradient Formation Under Differential Interstitial Fluid Flow Environments

10.20944/preprints202111.0353.v1 ◽

2021 ◽

Author(s):

Caleb Stine ◽

Jennifer Munson

Keyword(s):

Fluid Flow ◽

Interstitial Fluid ◽

Single Cells ◽

Specific Cell ◽

Minimal Distance ◽

Interstitial Flow ◽

Interstitial Fluid Flow ◽

Element Analysis ◽

Gradient Formation ◽

Fluid flow and chemokine gradients play a large part in not only regulating homeostatic processes in the brain, but also in pathologic conditions by directing cell migration. Tumor cells in particular are superior at invading into the brain resulting in tumor recurrence. One mechanism that governs cellular invasion is autologous chemotaxis, whereby pericellular chemokine gradients form due to interstitial fluid flow (IFF) leading cells to migrate up the gradient. Glioma cells have been shown to specifically use CXCL12 to increase their invasion under heightened interstitial flow. Computational modeling of this gradient offers better insight into the extent of its development around single cells, yet very few conditions have been modelled. In this paper, a computational model is developed to investigate how a CXCL12 gradient may form around a tumor cell and what conditions are necessary to affect its formation. Through finite element analysis using COMSOL and coupled convection-diffusion/mass transport equations, we show that velocity (IFF magnitude) has the largest parametric effect on gradient formation, multidirectional fluid flow causes gradient formation in the direction of the resultant which is governed by IFF magnitude, common treatments and flow patterns have a spatiotemporal effect on pericellular gradients, exogenous background concentrations can abrogate the autologous effect depending on how close the cell is to the source, that there is a minimal distance away from the tumor border required for a single cell to establish an autologous gradient, and finally that the development of a gradient formation is highly dependent on specific cell morphology.

Paravascular spaces at the brain surface: Low resistance pathways for cerebrospinal fluid flow

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x17737984 ◽

2017 ◽

Vol 38 (4) ◽

pp. 719-726 ◽

Cited By ~ 44

Author(s):

Beatrice Bedussi ◽

Mitra Almasian ◽

Judith de Vos ◽

Ed VanBavel ◽

Erik NTP Bakker

Keyword(s):

Cerebrospinal Fluid ◽

Fluid Flow ◽

Confocal Imaging ◽

Waste Products ◽

Low Resistance ◽

Cranial Window ◽

Brain Surface ◽

Antegrade Flow ◽

Clearance of waste products from the brain is of vital importance. Recent publications suggest a potential clearance mechanism via paravascular channels around blood vessels. Arterial pulsations might provide the driving force for paravascular flow, but its flow pattern remains poorly characterized. In addition, the relationship between paravascular flow around leptomeningeal vessels and penetrating vessels is unclear. In this study, we determined blood flow and diameter pulsations through a thinned-skull cranial window. We observed that microspheres moved preferentially in the paravascular space of arteries rather than in the adjacent subarachnoid space or around veins. Paravascular flow was pulsatile, generated by the cardiac cycle, with net antegrade flow. Confocal imaging showed microspheres distributed along leptomeningeal arteries, while their presence along penetrating arteries was limited to few vessels. These data suggest that paravascular spaces around leptomeningeal arteries form low resistance pathways on the surface of the brain that facilitate cerebrospinal fluid flow.

Autologous Gradient Formation under Differential Interstitial Fluid Flow Environments

Biophysica ◽

10.3390/biophysica2010003 ◽

2022 ◽

Vol 2 (1) ◽

pp. 16-33

Author(s):

Caleb A. Stine ◽

Jennifer M. Munson

Keyword(s):

Fluid Flow ◽

Interstitial Fluid ◽

Single Cells ◽

Specific Cell ◽

Interstitial Flow ◽

Interstitial Fluid Flow ◽

Element Analysis ◽

Convection Diffusion ◽

Gradient Formation ◽

Fluid flow and chemokine gradients play a large part in not only regulating homeostatic processes in the brain, but also in pathologic conditions by directing cell migration. Tumor cells in particular are superior at invading into the brain resulting in tumor recurrence. One mechanism that governs cellular invasion is autologous chemotaxis, whereby pericellular chemokine gradients form due to interstitial fluid flow (IFF) leading cells to migrate up the gradient. Glioma cells have been shown to specifically use CXCL12 to increase their invasion under heightened interstitial flow. Computational modeling of this gradient offers better insight into the extent of its development around single cells, yet very few conditions have been modelled. In this paper, a computational model is developed to investigate how a CXCL12 gradient may form around a tumor cell and what conditions are necessary to affect its formation. Through finite element analysis using COMSOL and coupled convection-diffusion/mass transport equations, we show that velocity (IFF magnitude) has the largest parametric effect on gradient formation, multidirectional fluid flow causes gradient formation in the direction of the resultant which is governed by IFF magnitude, common treatments and flow patterns have a spatiotemporal effect on pericellular gradients, exogenous background concentrations can abrogate the autologous effect depending on how close the cell is to the source, that there is a minimum distance away from the tumor border required for a single cell to establish an autologous gradient, and finally that the development of a gradient formation is highly dependent on specific cell morphology.

Network Analysis of Cerebrospinal Fluid Dynamics

10.1115/imece2001/bed-23126 ◽

2001 ◽

Author(s):

Lili Zheng ◽

Michael Egnor ◽

Keith Banninger

Keyword(s):

Fluid Dynamics ◽

Cerebrospinal Fluid ◽

Fluid Flow ◽

Network Analysis ◽

Progressive Increase ◽

Cerebrospinal Fluid Dynamics ◽

High Failure Rate ◽

Life Threatening ◽

Abstract Hydrocephalus is a group of life threatening disorders of cerebrospinal fluid flow in and around the brain. It is characterized, in most cases, by accumulation of cerebrospinal fluid in the ventricles of the brain and a progressive increase in pressure in the cranium. The etiology has traditionally been ascribed to an imbalance between the formation and absorption of the cerebrospinal fluid (CSF). Based on this understanding, the treatment is to insert a shunt surgically in order to drain the accumulating fluid in the heart or abdomen. This treatment is invasive and has a high failure rate.