Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Fluid dynamic principles for analysis of intracranial pressure control: application towards space medicine and hydrocephalus
Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
2019 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Fluiddynamiska principer för analys av intrakraniellt tryck och dess reglering : för tillämpning inom rymdmedicin och hydrocefalus (Swedish)
Abstract [en]

Intracranial pressure (ICP) is an important component of the fluid dynamic environment of the brain and plays a central role with regards to the maintenance of normal cerebral blood flow and neuronal function. However, many regulatory mechanisms controlling the ICP are still poorly understood. One major gap in knowledge in this regard is the mechanism behind the postural/gravitational control of ICP. This is partly due to the fact that most ICP investigations are performed with the patients in a supine or recumbent position. Since most people spend 16 hours a day in an upright position, understanding these mechanics is highly motivated. Also spurring research on this topic is the increasing number of reports of the spaceflight-associated neuro-ocular syndrome (SANS) found in astronauts after prolonged exposure to weightlessness (i.e. microgravity), where evidence suggests that a disrupted balance between ICP and intraocular pressure (IOP) may be an underlying cause. Understanding how ICP is regulated with respect to posture could therefore provide important insight into the alterations introduced by microgravity, where postural effects are removed, and how to improve the safety of astronauts who are susceptible to this syndrome. Here on earth, disturbances in the ICP or cerebrospinal fluid (CSF) dynamics are associated with the development of chronic neurological diseases. One particular disease of interest is communicating hydrocephalus, where the cerebral ventricles are enlarged despite the absence of macroscopic CSF flow obstructions. A common finding in these patients is that of altered pulsatile flow in the CSF. The overall aim of this thesis was to utilize fluid dynamic principles to describe and validate potential regulatory mechanisms behind postural changes in ICP and causes of ventriculomegaly. The thesis is based on four scientific papers (paper I—IV).

A postural dependency of the IOP-ICP pressure difference was verified by simultaneous measurements of ICP (assessed through lumbar puncture) and IOP (measured with an Applanation Resonance Tonometer) (paper I). Based on these measurements, a 24-hour average of the IOP-ICP pressure difference at the level of the eye was estimated for the state of microgravity, predicting a reduced pressure difference in space compared with that on earth.

A hypothesis where postural changes in ICP are described by hydrostatic effects in the venous system, and where these effects are altered by the collapse of the internal jugular veins (IJVs) in more upright positions, was evaluated (paper II and III). Using ultrasound data, it was shown that the venous hydrostatic pressure gradient was balanced by viscous pressure losses in the collapsed IJVs to uphold a near atmospheric pressure at the level of the neck in the upright posture (paper II). A full evaluation of the hypothesis was then performed, based on simultaneous assessment of ICP, central venous pressure (through a PICC-line) and venous collapse in 7 postures of upper-body tilt in healthy volunteers (paper III).The proposed description could accurately predict the general changes seen in the measured ICP for all investigated postures (mean difference: -0.03±2.7 mmHg or -4.0±360 Pa).

Pulsatile CSF flow-induced pressure differences between the ventricles and subarachnoid space were evaluated as a source for ventriculomegaly in communicating hydrocephalus (paper IV). The pressure distributions resulting from the pulsatile CSF flow were calculated using computational fluid dynamics based on MRI data. The estimated pressures revealed a net pressure difference (mean: 0.001±0.003 mmHg or 0.2±0.4 Pa, p=0.03) between the ventricles and the subarachnoid space, over the cardiac cycle, with higher pressure in the third and lateral ventricles.

In conclusion, the results of this thesis support venous hydrostatics and jugular venous collapse as key governing factors in the postural/gravitational control of ICP. Furthermore, a postural dependency of the IOP-ICP pressure difference was demonstrated, providing a potential explanation for how an imbalance between the pressure of the eye and brain can be introduced in microgravity. Computational fluid dynamic analysis revealed that the altered pulsations in communicating hydrocephalus generate a pressure gradient within the CSF system. However, the gradient was small and additional effects are probably needed to explain the ventriculomegaly in these patients. 

Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2019. , p. 67
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2018
Keywords [en]
Intracranial pressure, posture, cerebrospinal fluid, microgravity, venous collapse, internal jugular vein, fluid dynamics, venous pressure, spaceflight-associated neuro-ocular syndrome, hydrocephalus, mathematical modeling, ultrasound, magnetic resonance imaging
National Category
Physiology
Identifiers
URN: urn:nbn:se:umu:diva-157031ISBN: 978-91-7855-029-6 (print)OAI: oai:DiVA.org:umu-157031DiVA, id: diva2:1294184
Public defence
2019-03-29, Hörsal B, Unod T9, Norrlands Universitetssjukhus, Umeå, 13:00 (English)
Opponent
Supervisors
Funder
Swedish National Space BoardSwedish Research Council, grant 2015-05616Swedish Heart Lung Foundation, grant 20140592Available from: 2019-03-08 Created: 2019-03-06 Last updated: 2019-11-19Bibliographically approved
List of papers
1. The Pressure Difference between Eye and Brain Changes with Posture
Open this publication in new window or tab >>The Pressure Difference between Eye and Brain Changes with Posture
Show others...
2016 (English)In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 80, no 2, p. 269-276Article in journal (Refereed) Published
Abstract [en]

Objective: The discovery of a posture-dependent effect on the difference between intraocular pressure (IOP) and intracranial pressure (ICP) at the level of lamina cribrosa could have important implications for understanding glaucoma and idiopathic intracranial hypertension and could help explain visual impairments in astronauts exposed to microgravity. The aim of this study was to determine the postural influence on the difference between simultaneously measured ICP and IOP.

Methods: Eleven healthy adult volunteers (age = 46 ± 10 years) were investigated with simultaneous ICP, assessed through lumbar puncture, and IOP measurements when supine, sitting, and in 9° head-down tilt (HDT). The trans–lamina cribrosa pressure difference (TLCPD) was calculated as the difference between the IOP and ICP. To estimate the pressures at the lamina cribrosa, geometrical distances were estimated from magnetic resonance imaging and used to adjust for hydrostatic effects.

Results: The TLCPD (in millimeters of mercury) between IOP and ICP was 12.3 ± 2.2 for supine, 19.8 ± 4.6 for sitting, and 6.6 ± 2.5 for HDT. The expected 24-hour average TLCPD on earth—assuming 8 hours supine and 16 hours upright—was estimated to be 17.3mmHg. By removing the hydrostatic effects on pressure, a corresponding 24-hour average TLCPD in microgravity environment was simulated to be 6.7mmHg.

Interpretation: We provide a possible physiological explanation for how microgravity can cause symptoms similar to those seen in patients with elevated ICP. The observed posture dependency of TLCPD also implies that assessment of the difference between IOP and ICP in upright position may offer new understanding of the pathophysiology of idiopathic intracranial hypertension and glaucoma. 

National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-126335 (URN)10.1002/ana.24713 (DOI)000382402600010 ()27352140 (PubMedID)
Available from: 2016-10-25 Created: 2016-10-03 Last updated: 2019-03-06Bibliographically approved
2. Human jugular vein collapse in the upright posture: implications for postural intracranial pressure regulation
Open this publication in new window or tab >>Human jugular vein collapse in the upright posture: implications for postural intracranial pressure regulation
Show others...
2017 (English)In: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 14, article id 17Article in journal (Refereed) Published
Abstract [en]

Background: Intracranial pressure (ICP) is directly related to cranial dural venous pressure (P-dural). In the upright posture, P-dural is affected by the collapse of the internal jugular veins (IJVs) but this regulation of the venous pressure has not been fully understood. A potential biomechanical description of this regulation involves a transmission of surrounding atmospheric pressure to the internal venous pressure of the collapsed IJVs. This can be accomplished if hydrostatic effects are cancelled by the viscous losses in these collapsed veins, resulting in specific IJV cross-sectional areas that can be predicted from flow velocity and vessel inclination. Methods: We evaluated this potential mechanism in vivo by comparing predicted area to measured IJV area in healthy subjects. Seventeen healthy volunteers (age 45 +/- 9 years) were examined using ultrasound to assess IJV area and flow velocity. Ultrasound measurements were performed in supine and sitting positions. Results: IJV area was 94.5 mm(2) in supine and decreased to 6.5 +/- 5.1 mm(2) in sitting position, which agreed with the predicted IJV area of 8.7 +/- 5.2 mm(2) (equivalence limit +/- 5 mm(2), one-sided t tests, p = 0.03, 33 IJVs). Conclusions: The agreement between predicted and measured IJV area in sitting supports the occurrence of a hydrostatic-viscous pressure balance in the IJVs, which would result in a constant pressure segment in these collapsed veins, corresponding to a zero transmural pressure. This balance could thus serve as the mechanism by which collapse of the IJVs regulates P-dural and consequently ICP in the upright posture.

Place, publisher, year, edition, pages
BioMed Central, 2017
Keywords
Jugular vein, Collapse, Intracranial pressure, Posture, Physiology
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-137632 (URN)10.1186/s12987-017-0065-2 (DOI)000403482600001 ()28623925 (PubMedID)
Available from: 2017-07-18 Created: 2017-07-18 Last updated: 2019-03-06Bibliographically approved
3. Venous collapse regulates intracranial pressure in upright body positions
Open this publication in new window or tab >>Venous collapse regulates intracranial pressure in upright body positions
Show others...
2018 (English)In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 314, no 3, p. R377-R385Article in journal (Refereed) Published
Abstract [en]

Recent interest in intracranial pressure (ICP) in the upright posture has revealed that the mechanisms regulating postural changes in ICP are not fully understood. We have suggested an explanatory model where the postural changes in ICP depend on well-established hydrostatic effects in the venous system and where these effects are interrupted by collapse of the internal jugular veins (IJVs) in more upright positions. The aim of this study was to investigate this relationship by simultaneous invasive measurements of ICP, venous pressure and IJV collapse in healthy volunteers. ICP (monitored via the lumbar route), central venous pressure (PICC-line) and IJV cross-sectional area (ultrasound) were measured in 11 healthy volunteers (47±10 years) in seven positions, from supine to sitting (0°-69°). Venous pressure and anatomical distances were used to predict ICP in accordance with the explanatory model, and IJV area was used to assess IJV collapse. The hypothesis was tested by comparing measured ICP to predicted ICP. Our model accurately described the general behavior of the observed postural ICP changes (mean difference: -0.03±2.7 mmHg). No difference was found between predicted and measured ICP for any tilt-angle (p-values: 0.65 - 0.94). The results support the hypothesis that postural ICP changes are governed by hydrostatic effects in the venous system and IJV collapse. This improved understanding of the postural ICP regulation may have important implications for the development of better treatments for neurological and neurosurgical conditions affecting ICP.

Place, publisher, year, edition, pages
American Physiological Society, 2018
Keywords
Intracranial pressure, healthy volunteers, hydrocephalus, posture, venous pressure
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-142424 (URN)10.1152/ajpregu.00291.2017 (DOI)000426326500006 ()29118021 (PubMedID)
Available from: 2017-11-30 Created: 2017-11-30 Last updated: 2019-03-06Bibliographically approved
4. Can pulsatile CSF flow across the cerebral aqueduct cause ventriculomegaly?: A prospective study of patients with communicating hydrocephalus.
Open this publication in new window or tab >>Can pulsatile CSF flow across the cerebral aqueduct cause ventriculomegaly?: A prospective study of patients with communicating hydrocephalus.
2019 (English)In: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 16, no 1, article id 40Article in journal (Refereed) Published
Abstract [en]

Background: Communicating hydrocephalus is a disease where the cerebral ventricles are enlarged. It is characterized by the absence of detectable cerebrospinal fluid (CSF) outflow obstructions and often with increased CSF pulsatility measured in the cerebral aqueduct (CA). We hypothesize that the cardiac-related pulsatile flow over the CA, with fast systolic outflow and slow diastolic inflow, can generate net pressure effects that could source the ventriculomegaly in these patients. This would require a non-zero cardiac cycle averaged net pressure difference (ΔPnet) over the CA, with higher average pressure in the lateral and third ventricles.

Methods: We tested the hypothesis by calculating ΔPnet across the CA using computational fluid dynamics based on prospectively collected high-resolution structural (FIESTA-C, resolution 0.39 × 0.39 × 0.3 mm3) and velocimetric (2D-PCMRI, in-plane resolution 0.35 × 0.35 mm2) MRI-data from 30 patients investigated for communicating hydrocephalus.

Results: The ΔPnet due to CSF pulsations was non-zero for the study group (p = 0.03) with a magnitude of 0.2 ± 0.4 Pa (0.001 ± 0.003 mmHg), with higher pressure in the third ventricle. The maximum pressure difference over the cardiac cycle ΔPmax was 20.3 ± 11.8 Pa and occurred during systole. A generalized linear model verified an association between ΔPnet and CA cross-sectional area (p = 0.01) and flow asymmetry, described by the ratio of maximum inflow/outflow (p = 0.04), but not for aqueductal stroke volume (p = 0.35).

Conclusions: The results supported the hypothesis with respect to the direction of ΔPnet, although the magnitude was low. Thus, although the pulsations may generate a pressure difference across the CA it is likely too small to explain the ventriculomegaly in communicating hydrocephalus.

Place, publisher, year, edition, pages
BioMed Central, 2019
Keywords
Communicating hydrocephalus, computational fluid dynamics, cerebrospinal fluid pressure, brain imaging, cerebral aqueduct
National Category
Medical Engineering
Identifiers
urn:nbn:se:umu:diva-157029 (URN)10.1186/s12987-019-0159-0 (DOI)000504082400001 ()31865917 (PubMedID)
Funder
Swedish National Space BoardSwedish Research Council, grant 2015-05616Swedish Heart Lung Foundation, grant 20140592
Note

Originally included in thesis in manuscript form

Available from: 2019-03-06 Created: 2019-03-06 Last updated: 2020-01-09Bibliographically approved

Open Access in DiVA

fulltext(4880 kB)111 downloads
File information
File name FULLTEXT01.pdfFile size 4880 kBChecksum SHA-512
879a82c4ac6b4c431e79cb694d974c4f75f0bdd57f86bfd1e1c7bfe29cae9e4ca2cd4b5a310aba291538b44880bdf21da8cfb55f1c325688b65246dc707c69e6
Type fulltextMimetype application/pdf
spikblad(165 kB)14 downloads
File information
File name SPIKBLAD01.pdfFile size 165 kBChecksum SHA-512
79c1ca5d9993a34c3f9f419bcaaa94038aa3ad67b99caf2bbab2e9b149b46fbe236349508f40d9bca25574332f4dced74ca51cf793dd2024e4f0122f6f779582
Type spikbladMimetype application/pdf

Search in DiVA

By author/editor
Holmlund, Petter
By organisation
Department of Radiation SciencesClinical Neuroscience
Physiology

Search outside of DiVA

GoogleGoogle Scholar
Total: 111 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 878 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf