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Holmlund, Petter
Publications (7 of 7) Show all publications
Holmlund, P. (2019). Fluid dynamic principles for analysis of intracranial pressure control: application towards space medicine and hydrocephalus. (Doctoral dissertation). Umeå: Umeå Universitet
Open this publication in new window or tab >>Fluid dynamic principles for analysis of intracranial pressure control: application towards space medicine and hydrocephalus
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Fluiddynamiska principer för analys av intrakraniellt tryck och dess reglering : för tillämpning inom rymdmedicin och hydrocefalus
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
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:nbn:se:umu:diva-157031 (URN)978-91-7855-029-6 (ISBN)
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 20140592
Available from: 2019-03-08 Created: 2019-03-06 Last updated: 2019-03-07Bibliographically approved
Westlund, A., Holmlund, P., Johansson, E., Malm, J. & Eklund, A. (2019). Semi-automatic method for segmentation of the internal jugular vein in ultrasound movies evaluated at different body postures. Biomedical Physics & Engineering Express, 5(4), Article ID 045034.
Open this publication in new window or tab >>Semi-automatic method for segmentation of the internal jugular vein in ultrasound movies evaluated at different body postures
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2019 (English)In: Biomedical Physics & Engineering Express, E-ISSN 2057-1976, Vol. 5, no 4, article id 045034Article in journal (Refereed) Published
Abstract [en]

Objective: The collapse of the internal jugular vein (IJV) regulates intracranial pressure (ICP) in upright body positions. The cross-section area (CSA) is therefore of interest when studying the effects of postural changes in various neurological diseases. We have developed a semi-automatic segmentation method, which tracks the CSA of the IJV in ultrasound movies, and evaluated its performance in three body positions (supine, 16°, 71°). Approach: The proposed method utilized post-processing image filtering combined with a modified snake active contour algorithm. The ultrasound movies were retrospectively analysed (n = 231, 3s, 28 fps) based on previously collected data from 17 healthy volunteers. The computed CSAs (CA) from the segmentation method were compared to manually segmented CSAs (MA) in two frames per movie. Tracking performance were evaluated by visual inspection. Main results: In the supine position, 100% of the ultrasound movies were tracked successfully, and the mean of CA-MA was −4.4 ± 6.9 mm2 (MA, 88.4 ± 50.5 mm2). The most challenging movies occurred in upright body posture where tracking success rate was 90% and mean of CA-MA was −1.4 ± 2.2 mm2 (MA, 12.0 ± 11.1 mm2). The semi-automatic segmentations took 55 s to perform on average (per movie) compared to manual segmentations which took 50 min. Significance: Segmentations made by the proposed method were comparable to manual segmentations in all tilt-angles, however much faster. Efficient and accurate tracking of the CSA of the IJV, with respect to postural changes, could help furthering our understanding of how IJV-biomechanics relates to regulation of intracranial pressure in different neurological diseases and physiological states.

Place, publisher, year, edition, pages
Institute of Physics Publishing (IOPP), 2019
Keywords
posture, intracranial pressure, ultrasound, jugular veins, computer-assisted image analysis
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-161912 (URN)10.1088/2057-1976/ab285e (DOI)000475798800001 ()
Available from: 2019-08-07 Created: 2019-08-07 Last updated: 2019-08-07Bibliographically approved
Holmlund, P., Eklund, A., Koskinen, L.-O. D., Johansson, E., Sundström, N., Malm, J. & Qvarlander, S. (2018). Venous collapse regulates intracranial pressure in upright body positions. American Journal of Physiology. Regulatory Integrative and Comparative Physiology, 314(3), R377-R385
Open this publication in new window or tab >>Venous collapse regulates intracranial pressure in upright body positions
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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
Holmlund, P., Johansson, E., Qvarlander, S., Wåhlin, A., Ambarki, K., Koskinen, L.-O. D., . . . Eklund, A. (2017). Human jugular vein collapse in the upright posture: implications for postural intracranial pressure regulation. Fluids and Barriers of the CNS, 14, Article ID 17.
Open this publication in new window or tab >>Human jugular vein collapse in the upright posture: implications for postural intracranial pressure regulation
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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
Holmlund, P., Johansson, E., Qvarlander, S., Wåhlin, A., Ambarki, K., Koskinen, L.-O. D., . . . Eklund, A. (2017). Jugular vein collapse in upright and its relation to intracranial pressure regulation. Paper presented at 28th International Symposium on Cerebral Blood Flow, Metabolism and Function / 13th International Conference on Quantification of Brain Function with PET, APR 01-04, 2017, Int Soc Cerebral Blood Flow & Metab, Berlin, GERMANY. Journal of Cerebral Blood Flow and Metabolism, 37, 297-297
Open this publication in new window or tab >>Jugular vein collapse in upright and its relation to intracranial pressure regulation
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2017 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, p. 297-297Article in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
SAGE PUBLICATIONS INC, 2017
National Category
Physiology Neurosciences
Identifiers
urn:nbn:se:umu:diva-136208 (URN)000400157400425 ()
Conference
28th International Symposium on Cerebral Blood Flow, Metabolism and Function / 13th International Conference on Quantification of Brain Function with PET, APR 01-04, 2017, Int Soc Cerebral Blood Flow & Metab, Berlin, GERMANY
Note

Supplement: 1 Meeting Abstract: PS03-082

Available from: 2017-07-03 Created: 2017-07-03 Last updated: 2019-05-20Bibliographically approved
Eklund, A., Jóhannesson, G., Johansson, E., Holmlund, P., Qvarlander, S., Ambarki, K., . . . Malm, J. (2016). The Pressure Difference between Eye and Brain Changes with Posture. Annals of Neurology, 80(2), 269-276
Open this publication in new window or tab >>The Pressure Difference between Eye and Brain Changes with Posture
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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
Holmlund, P., Qvarlander, S., Malm, J. & Eklund, A.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.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Communicating hydrocephalus is a disease where the cerebral ventricles are enlarged. It is characterized by the absence of 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 cerebral aqueduct (CA), with fast systolic outflow and slow diastolic inflow, can generate net pressure effects that could source the ventriculomegaly in these patients. Our hypothesis predicts a cardiac cycle averaged net pressure difference (ΔPnet) over the CA, with higher average pressure in the lateral and third ventricles. We tested the hypothesis by calculating ΔPnetacross the CA using computational fluid dynamics (CFD) based on prospectively collected high-resolution structural (FIESTA-C, resolution 0.39x0.39x0.3mm3) and velocimetric (2D-PCMRI, in-plane resolution 0.35x0.35mm2) MRI-data from 30 patients investigated for communicating hydrocephalus. The ΔPnetdue to CSF pulsations was non-zero for the study group (p=0.03) with a magnitude of 0.2±0.4 Pa, with higher pressure in the third ventricle. The maximum pressure difference over the cardiac cycle ΔPmaxwas 20.3±11.8 Pa and occurred during systole. A generalized linear model verified an association between ΔPnetand 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). The results thus supported the hypothesis with respect to the direction of ΔPnet, although the magnitude was low. This indicates that although the pulsations do generate a pressure difference across the CA it is likely too small to explain the ventriculomegaly in communicating hydrocephalus.

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)
Funder
Swedish National Space BoardSwedish Research Council, grant 2015-05616Swedish Heart Lung Foundation, grant 20140592
Available from: 2019-03-06 Created: 2019-03-06 Last updated: 2019-03-07
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