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  • 1.
    Eklund, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Holmlund, Petter
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    The Pressure Difference between Eye and Brain Changes with Posture2016Ingår i: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 80, nr 2, s. 269-276Artikel i tidskrift (Refereegranskat)
    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. 

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  • 2.
    Holmgren, Madelene
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Holmlund, Petter
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Stoverud, Karen-Helene
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Department of Health Research, SINTEF Digital, NO, Trondheim, Norway.
    Zarrinkoob, Laleh
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Wåhlin, Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Prediction of cerebral perfusion pressure during carotid surgery: A computational fluid dynamics approach2022Ingår i: Clinical Biomechanics, ISSN 0268-0033, E-ISSN 1879-1271, Vol. 100, artikel-id 105827Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Maintaining cerebral perfusion pressure in the brain when a carotid artery is closed during vascular surgery is critical for avoiding intraoperative hypoperfusion and risk of ischemic stroke. Here we propose and evaluate a method based on computational fluid dynamics for predicting patient-specific cerebral perfusion pressures at carotid clamping during carotid endarterectomy.

    Methods: The study consisted of 22 patients with symptomatic carotid stenosis who underwent carotid endarterectomy (73 ± 5 years, 59–80 years, 17 men). The geometry of the circle of Willis was obtained preoperatively from computed tomography angiography and corresponding flow rates from four-dimensional flow magnetic resonance imaging. The patients were also classified as having a present or absent ipsilateral posterior communicating artery based on computed tomography angiography. The predicted mean stump pressures from computational fluid dynamics were compared with intraoperatively measured stump pressures from carotid endarterectomy.

    Findings: On group level, there was no difference between the predicted and measured stump pressures (−0.5 ± 13 mmHg, P = 0.86) and the pressures were correlated (r = 0.44, P = 0.039). Omitting two outliers, the correlation increased to r = 0.78 (P < 0.001) (−1.4 ± 8.0 mmHg, P = 0.45). Patients with a present ipsilateral posterior communicating artery (n = 8) had a higher measured stump pressure than those with an absent artery (n = 12) (P < 0.001).

    Interpretation: The stump pressure agreement indicates that the computational fluid dynamics approach was promising in predicting cerebral perfusion pressures during carotid clamping, which may prove useful in the preoperative planning of vascular interventions.

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  • 3.
    Holmgren, Madelene
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Holmlund, Petter
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Støverud, Karen-Helene
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Zarrinkoob, Laleh
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Computational fluid dynamics for prediction of measured carotid stump pressure during carotid endarterectomyManuskript (preprint) (Övrigt vetenskapligt)
  • 4.
    Holmlund, Petter
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Fluid dynamic principles for analysis of intracranial pressure control: application towards space medicine and hydrocephalus2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    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. 

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  • 5.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Venous collapse regulates intracranial pressure in upright body positions2018Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 314, nr 3, s. R377-R385Artikel i tidskrift (Refereegranskat)
    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.

  • 6.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Human jugular vein collapse in the upright posture: implications for postural intracranial pressure regulation2017Ingår i: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 14, artikel-id 17Artikel i tidskrift (Refereegranskat)
    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.

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  • 7.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jugular vein collapse in upright and its relation to intracranial pressure regulation2017Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, s. 297-297Artikel i tidskrift (Refereegranskat)
  • 8.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Can pulsatile CSF flow across the cerebral aqueduct cause ventriculomegaly?: A prospective study of patients with communicating hydrocephalus.2019Ingår i: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 16, nr 1, artikel-id 40Artikel i tidskrift (Refereegranskat)
    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.

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  • 9.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Stoverud, Karen-Helene
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Department of Health Research, SINTEF Digital, Trondheim, Norway.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Mathematical modelling of the CSF system: effects of microstructures and posture on optic nerve subarachnoid space dynamics2022Ingår i: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 19, nr 1, artikel-id 67Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The pressure difference between the eye and brain in upright postures may be affected by compartmentalization of the optic nerve subarachnoid space (ONSAS). Both pressure and deformation will depend on the microstructures of the ONSAS, and most likely also on ocular glymphatic clearance. Studying these factors could yield important knowledge regarding the translaminar pressure difference, which is suspected to play a role in normal-tension glaucoma.

    Methods: A compartment model coupling the ONSAS with the craniospinal CSF system was used to investigate the effects of microstructures on the pressure transfer through the ONSAS during a posture change from supine to upright body postures. ONSAS distensibility was based on MRI measurements. We also included ocular glymphatic flow to investigate how local pressure gradients alter this flow with changes in posture.

    Results: A compartmentalization of the ONSAS occurred in the upright posture, with ONSAS porosity (degree of microstructural content) affecting the ONSAS pressure (varying the supine/baseline porosity from 1.0 to 0.75 yielded pressures between − 5.3 and − 2 mmHg). Restricting the minimum computed porosity (occurring in upright postures) to 0.3 prevented compartmentalization, and the ONSAS pressure could equilibrate with subarachnoid space pressure (− 6.5 mmHg) in ≤ 1 h. The ocular glymphatics analysis predicted that substantial intraocular-CSF flows could occur without substantial changes in the ONSAS pressure. The flow entering the ONSAS in supine position (both from the intraocular system and from the cranial subarachnoid space) exited the ONSAS through the optic nerve sheath, while in upright postures the flow through the ONSAS was redirected towards the cranial subarachnoid space.

    Conclusions: Microstructures affect pressure transmission along the ONSAS, potentially contributing to ONSAS compartmentalization in upright postures. Different pathways for ocular glymphatic flow were predicted for different postures.

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  • 10.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Stoverud, Karen-Helene
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Author Response: Posture-Dependent Collapse of the Optic Nerve Subarachnoid Space: A Combined MRI and Modeling Study2021Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 62, nr 15, artikel-id 15Artikel i tidskrift (Övrigt vetenskapligt)
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  • 11.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Stoverud, Karen-Helene
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Posture-dependent collapse of the optic nerve subarachnoid space: A combined MRI and modeling study2021Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 62, nr 4, artikel-id 26Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: We hypothesize that a collapse of the optic nerve subarachnoid space (ONSAS) in the upright posture may protect the eyes from large translamina cribrosa pressure differences (TLCPD) believed to play a role in various optic nerve diseases (e.g., glaucoma). In this study, we combined magnetic resonance imaging (MRI) and mathematical modeling to investigate this potential ONSAS collapse and its effects on the TLCPD.

    METHODS: First, we performed MRI on six healthy volunteers in 6° head-down tilt (HDT) and 13° head-up tilt (HUT) to assess changes in ONSAS volume (measured from the eye to the optic canal) with changes in posture. The volume change reflects optic nerve sheath (ONS) distensibility. Second, we used the MRI data and mathematical modeling to simulate ONSAS pressure and the potential ONSAS collapse in a 90° upright posture.

    RESULTS: The MRI showed a 33% decrease in ONSAS volume from the HDT to HUT (P < 0.001). In the upright posture, the simulations predicted an ONSAS collapse 25 mm behind lamina cribrosa, disrupting the pressure communication between the ONSAS and the intracranial subarachnoid space. The collapse reduced the simulated postural increase in TLCPD by roughly 1 mm Hg, although this reduction was highly sensitive to ONS distensibility, varying between 0 and 4.8 mm Hg when varying the distensibility by ± 1 SD.

    CONCLUSIONS: The ONSAS volume along the optic nerve is posture dependent. The simulations supported the hypothesized ONSAS collapse in the upright posture and showed that even small changes in ONS stiffness/distensibility may affect the TLCPD.

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  • 12.
    Kristiansen, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Holmlund, Petter
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Linden, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Department of Ophthalmology, University of Iceland, Reykjavik, Iceland.
    Optic nerve subarachnoid space posture dependency: an MRI study in subjects with normal tension glaucoma and healthy controls2023Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 64, nr 15, artikel-id 20Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The purpose of this study was to examine the differences of optic nerve subarachnoid space (ONSAS) volume in patients with normal tension glaucoma (NTG) and healthy controls in different body positions.

    Methods: Eight patients with NTG and seven healthy controls underwent magnetic resonance imaging (MRI) examinations in head up tilt (HUT) +11 degrees and head down tilt (HDT) -5 degrees positions according to a randomized protocol determining the starting position. The ONSAS volume in both body positions was measured and compared between the two groups. The results were analyzed using a generalized linear model.

    Results: Between HDT and HUT, the postural ONSAS volume change was dependent on starting position (P < 0.001) and group (P = 0.003, NTG versus healthy). A subgroup analysis of those that were randomized to HUT examination first, coming directly from an upright position, showed that the patients with NTG had significantly larger positional ONSAS volume changes compared to the healthy controls; 121 ± 22 µL vs. 65 ± 37 µL (P = 0.049). Analysis of the ONSAS volume distribution showed different profiles for patients with NTG and healthy controls.

    Conclusions: There was a significant difference in ONSAS volume change between patients with NTG and healthy subjects when subjected to posture changes, specifically when going from upright to head-down posture. This indicates that patients with NTG had been exposed to a lower ONSAS pressure when they came from the upright posture, which suggests an increased translaminar pressure difference in upright position. This may support the theory that NTG has a dysfunction in an occlusion mechanism of the optic nerve sheath that could cause abnormally negative ONSAS pressures in upright posture.

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  • 13.
    Nilsson, Daniel
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Holmgren, Madelene
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Holmlund, Petter
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Dahlberg, Tobias
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Wiklund, Krister
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Andersson, Magnus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Patient-specific brain arteries molded as a flexible phantom model using 3D printed water-soluble resin2022Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, artikel-id 10172Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Visualizing medical images from patients as physical 3D models (phantom models) have many roles in the medical field, from education to preclinical preparation and clinical research. However, current phantom models are generally generic, expensive, and time-consuming to fabricate. Thus, there is a need for a cost- and time-efficient pipeline from medical imaging to patient-specific phantom models. In this work, we present a method for creating complex 3D sacrificial molds using an off-the-shelf water-soluble resin and a low-cost desktop 3D printer. This enables us to recreate parts of the cerebral arterial tree as a full-scale phantom model (10×6×410×6×4 cm) in transparent silicone rubber (polydimethylsiloxane, PDMS) from computed tomography angiography images (CTA). We analyzed the model with magnetic resonance imaging (MRI) and compared it with the patient data. The results show good agreement and smooth surfaces for the arteries. We also evaluate our method by looking at its capability to reproduce 1 mm channels and sharp corners. We found that round shapes are well reproduced, whereas sharp features show some divergence. Our method can fabricate a patient-specific phantom model with less than 2 h of total labor time and at a low fabrication cost.

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  • 14.
    Wahlin, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Holmlund, Petter
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Fellows, Abigail M.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Buckey, Jay C.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Re: Wahlin et al.: Optic nerve length before and after spaceflight [REPLY]2021Ingår i: Ophthalmology, ISSN 0161-6420, E-ISSN 1549-4713, Vol. 128, nr 5, s. E28-E28Artikel i tidskrift (Övrigt vetenskapligt)
  • 15.
    Westlund, Arvid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Holmlund, Petter
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Semi-automatic method for segmentation of the internal jugular vein in ultrasound movies evaluated at different body postures2019Ingår i: Biomedical Engineering & Physics Express, E-ISSN 2057-1976, Vol. 5, nr 4, artikel-id 045034Artikel i tidskrift (Refereegranskat)
    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.

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  • 16.
    Wåhlin, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Holmlund, Petter
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Fellows, Abigail M
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Buckey, Jay C
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Optic Nerve Length before and after Spaceflight2021Ingår i: Ophthalmology, ISSN 0161-6420, E-ISSN 1549-4713, Vol. 128, nr 2, s. 309-316Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: The spaceflight-associated neuro-ocular syndrome (SANS) affects astronauts on missions to the International Space Station (ISS). The SANS has blurred vision and ocular changes as typical features. The objective of this study was to investigate if microgravity can create deformations or movements of the eye or optic nerve, and if such changes could be linked to SANS.

    DESIGN: Cohort study.

    PARTICIPANTS: Twenty-two astronauts (age 48 ± 4 years).

    METHODS: The intervention consisted of time in microgravity at the ISS. We co-registered pre- and postspaceflight magnetic resonance imaging (MRI) scans and generated centerline representations of the optic nerve. The coordinates for the optic nerve head (ONH) and optic chiasm (OC) ends of the optic nerve were recorded along with the entire centerline path.

    MAIN OUTCOME MEASURES: Optic nerve length, ONH movement, and OC movement after time in microgravity.

    RESULTS: Optic nerve length increased (0.80 ± 0.74 mm, P < 0.001), primarily reflecting forward ONH displacement (0.63 ± 0.53 mm, P < 0.001). The forward displacement was positively related to mission duration, preflight body weight, and clinical manifestations of SANS. We also detected upward displacement of the OC (0.39 ± 0.50 mm, P = 0.002), indicative of brain movement, but this observation could not be linked to SANS.

    CONCLUSIONS: The spaceflight-induced optic nerve lengthening and anterior movement of the ONH support that SANS is caused by an altered pressure difference between the brain and the eye, leading to a forward push on the posterior of the eye. Body weight is a potential contributing risk factor. Direct assessment of intracranial pressure in space is required to verify the implicated mechanism behind the ocular findings in SANS.

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