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  • 101.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology. Neurologi.
    Andersson, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ågren-Wilsson, Aina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology. Neurologi.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery. Neurokirurgi.
    Koskinen, Lars-Owe D
    Neurokirurgi.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology. Neurologi.
    Cerebrospinal fluid pulse pressure method: a possible substitute for the examination of B waves2004In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 101, no 6, p. 944-950Article in journal (Refereed)
    Abstract [en]

    Object. The appearance of numerous B waves during intracranial pressure (ICP) registration in patients with idiopathic adult hydrocephalus syndrome (IAHS) is considered to predict good outcome after shunt surgery. The aim of this study was to describe which physical parameters of the cerebrospinal fluid (CSF) system B-waves reflect and to find a method that could replace long-term B-wave analysis.

    Methods. Ten patients with IAHS were subjected to long-term registration of ICP and a lumbar constant-pressure infusion test. The B-wave presence, CSF outflow resistance (Rout), and relative pulse pressure coefficient (RPPC) were assessed using computerized analysis. The RPPC was introduced as a parameter reflecting the joint effect of elastance and pulsatory volume changes on ICP and was determined by relating ICP pulse amplitudes to mean ICP.

    Conclusions. The B-wave presence on ICP registration correlates strongly with RPPC (r = 0.91, p < 0.001, 10 patients) but not with CSF Rout. This correlation indicates that B waves—like RPPC—primarily reflect the ability of the CSF system to reallocate and store liquid rather than absorb it. The RPPC-assessing lumbar short-term CSF pulse pressure method could replace the intracranial long-term B-wave analysis.

  • 102.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hansson, William
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Three-day CSF drainage barely reduces ventricular size in normal pressure hydrocephalus2012In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 79, no 3, p. 237-242Article in journal (Refereed)
    Abstract [en]

    Objective: External lumbar drainage (ELD) of CSF is a test to determine the suitability of a shunt for patients with normal pressure hydrocephalus (NPH), but its effect on ventricular volume is not known. This study investigates the effect of 3-day ELD of 500 mL on ventricular size and clinical features in patients with idiopathic NPH.

    Methods: Fifteen patients were investigated in a 1.5-T MRI scanner before and after ELD. Ventricular volume was measured manually. Clinical features involved motor and cognitive functions, testing primarily gait and attention. Reduction in ventricular volume was correlated to total drain volume and clinical parameters. Statistical tests were nonparametric, and p < 0.05 was required for significance.

    Results: Drain volume was 415 mL (median 470 mL, range 160-510 mL). Ventricular size was reduced in all patients, averaging 3.7 mL (SD 2.2 mL, p < 0.001), which corresponded to a 4.2% contraction. The ratio of volume contraction to drain volume was only 0.9%. Seven patients improved in gait and 6 in attention. Ventricular reduction and total drain volume correlated neither with improvement nor with each other. The 7 patients with the largest drain volumes (close to 500 mL), had ventricular changes varying from 1.3 to 7.5 mL.

    Conclusions: Clinical improvement occurs in patients with NPH after ELD despite unaltered ventricles, suggesting that ventricular size is of little relevance for postshunt improvement or determining shunt function. The clinical effect provided by ELD, mimicking shunting, is probably related to the recurring CSF extractions rather than to the cumulative effect of the drainage on ventricular volume. Neurology(R) 2012;79:237-242

  • 103.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hauksson, Jon
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Improvement after cerebrospinal fluid drainage is related to levels of N-acetyl-aspartate in idiopathic normal pressure hydrocephalus2008In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 62, no 1, p. 135-142Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: This study uses proton magnetic resonance spectroscopy to investigate whether or not idiopathic normal pressure hydrocephalus is associated with neuronal dysfunction or ischemia in the brain. We evaluate whether or not proton magnetic resonance spectroscopy is useful for predicting improvement after long-term external lumbar drainage (ELD) of cerebrospinal fluid.

    METHODS: Eighteen patients (mean age, 73 yr; six women) and 10 matching controls participated. Participants were characterized by clinical features, cognitive and motor function tests, and cerebrospinal fluid hydrodynamics (patients only). Signals from N-acetyl-aspartate (NAA), choline, lactate, and creatine (Cr) (reference) were sampled once in controls and twice in patients (before and after a 3-day ELD of approximately 135 mL/24 h) by proton magnetic resonance spectroscopy (1.5 T) from a 7.2-mL volume in the frontal white matter. Improvement was defined by video recordings of the patients' gait.

    RESULTS: Sixteen patients finished the ELD (one patient had meningitis, and one patient had catheter insertion failure) with a mean drain volume of 395 mL. NAA/Cr ratios were lower in patients than in controls (1.60 versus 1.84, P = 0.02), but no difference was found for choline/Cr ratios. No lactate signals were detected. Fifty percent of patients improved after ELD. They had higher NAA/Cr ratios than nonimproved patients (1.70 versus 1.51, P = 0.01), but no differences were found in choline/Cr ratios or drain volume.

    CONCLUSION: NAA/Cr ratios were decreased in patients with idiopathic normal pressure hydrocephalus, which is consistent with neuronal dysfunction in the frontal white matter. Improved patients had NAA/Cr ratios close to normal, indicating that enough functional neurons are a prerequisite for the cerebrospinal fluid drainage to have an effect.

  • 104.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Koskinen, L-O D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    CSF pressure assessed by lumbar puncture agrees with intracranial pressure.2007In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 68, no 2, p. 155-158Article in journal (Refereed)
    Abstract
  • 105.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Idiopathic normal pressure hydrocephalus: increased supplementary motor activity accounts for improvement after CSF drainage.2008In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 131, no Pt 11, p. 2904-2912Article in journal (Refereed)
    Abstract [en]

    In patients with idiopathic normal pressure hydrocephalus (INPH), the changes in brain function that take place in conjunction with improved behavioural performance after CSF drainage is still unknown. In this study, we use functional MRI (fMRI) to investigate the changes in cortical activity that accompany improved motor and cognitive performance after long-term external lumbar drainage (ELD) of CSF in patients with INPH. Eighteen INPH patients were initially included together with age- and sex-matched controls. Data from 11 INPH patients were analysed both before and after ELD. The average drain volume for these 11 patients was 400 ml/3 days. Brain activation was investigated by fMRI before and after the procedure on a 1.5T Philips scanner using protocols taxing motor performance (finger tapping and reaction time) and cognitive functioning (memory and attention). Behavioural data were compared using non-parametric tests at a significance level of 0.05, whereas fMRI data were analysed by statistical parametric mapping including conjunction analysis of areas with enhanced activity after drainage in patients and areas activated in controls (P < 0.005, uncorrected). Improved regions were defined as areas in the INPH brain that increased in activity after ELD with the requirement that the same areas were activated in control subjects. Following ELD, right-hand finger tapping improved from 104 +/- 38 to 117 +/- 25 (mean +/- SD) (P = 0.02). Left-hand finger tapping showed a tendency to improve, the number of keystrokes increasing from 91 +/- 40 to 105 +/- 20 (P = 0.12). Right-hand reaction time improved from 1630 +/- 566 ms to 1409 +/- 442 ms, whereas left-hand reaction time improved from 1760 +/- 600 ms to 1467 +/- 420 ms (both P-values = 0.01). Significant improvements in motor performance were accompanied by bilateral increased activation in the supplementary motor area. No improvement was found in cognitive functioning. The results suggest that motor function recovery in INPH patients after CSF removal is related to enhanced activity in medial parts of frontal motor areas considered crucial for motor planning; a finding consistent with INPH being a syndrome related to a reversible suppression of frontal periventricular cortico-basal ganglia-thalamo-cortical pathways.

  • 106.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Diffusion tensor imaging reveals supplementary lesions to frontal white matter in Idiopathic normal pressure hydrocephalus2011In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 68, no 6, p. 1586-1593Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:: Idiopathic normal pressure hydrocephalus (INPH) is associated with white matter lesions, but the extent and severity of the lesions do not cohere with symptoms or improvement after shunting, implying the presence of further, yet undisclosed, injuries to white matter in INPH. OBJECTIVE:: To apply diffusion tensor imaging (DTI) to explore white matter lesions in patients with INPH before and after drainage of cerebrospinal fluid (CSF). METHODS:: Eighteen patients and ten controls were included. DTI was performed in a 1.5T MRI scanner before and after three-day drainage of 400 ml of CSF. Regions of interest included corpus callosum, capsula interna, frontal and lateral periventricular white matter, and centrum semiovale. White matter integrity was quantified by assessing fractional anisotropies (FA) and apparent diffusion coefficients (ADC), comparing them between patients and controls and between patients before and after drainage. The significance level corresponded to 0.05 (Bonferroni corrected). RESULTS:: Decreased FA in patients was found in three regions (p<0.002, p<0.001 and p<0.0001) in anterior frontal white matter, whereas elevated ADC was found in genu corpus callosum (p<0.0001) and areas of centrum semiovale associated to the precentral gyri (p<0.002). Diffusion patterns in these areas did not change after drainage. CONCLUSION:: DTI reveals subtle injuries - interpreted as axonal loss and gliosis - to anterior frontal white matter where high-order motor systems between frontal cortex and basal ganglia travel, further supporting the notion that motor symptoms in INPH are caused by a chronic ischemia to the neuronal systems involved in the planning processes of movements.

  • 107.
    Lindahl, O A
    et al.
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Constantinou, C E
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Murayama, Y
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Omata, S
    Tactile resonance sensors in medicine.2009In: Journal of Medical Engineering & Technology, ISSN 0309-1902, E-ISSN 1464-522X, Vol. 33, no 4, p. 263-273Article in journal (Refereed)
    Abstract [en]

    Tactile sensors in general are used for measuring the physical parameters associated with contact between sensor and object. Tactile resonance sensors in particular are based on the principle of measuring the frequency shift, Deltaf, defined as the difference between a freely vibrating sensor resonance frequency and the resonance frequency measured when the sensor makes contact to an object. Deltaf is therefore related to the acoustic impedance of the object and can be used to characterize its material properties. In medicine, tactile resonance sensor systems have been developed for the detection of cancer, human ovum fertility, eye pressure and oedema. In 1992 a Japanese research group published a paper presenting a unique phase shift circuit to facilitate resonance measurements. In this review we summarize the current state-of-the-art of tactile resonance sensors in medicine based on the phase shift circuit and discuss the relevance of the measured parameters for clinical diagnosis. Future trends and applications enabled by this technology are also predicted.

  • 108.
    Lindén, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Östlund, Fanny
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Normal-Tension Glaucoma Has Normal Intracranial Pressure: A Prospective Study of Intracranial Pressure and Intraocular Pressure in Different Body Positions2018In: Ophthalmology, ISSN 0161-6420, E-ISSN 1549-4713, Vol. 125, no 3, p. 361-368Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To test the hypothesis that normal-tension glaucoma (NTG) is caused by an increased pressure difference across the lamina cribrosa (LC) related to a low intracranial pressure (ICP).

    DESIGN: Prospective case-control study.

    PARTICIPANTS: Thirteen NTG patients (9 women; median 71 [range: 56-83] years) were recruited for investigation with the same protocol as 11 healthy volunteers (8 women; 47 [30-59] years). A larger control group (n = 51; 30 women; 68 [30-81] years) was used only for ICP comparison in supine position.

    METHODS: ICP and intraocular pressure (IOP) were simultaneously measured in supine, sitting, and 9° head-down tilt (HDT) positions. Trans-lamina cribrosa pressure difference (TLCPD) was calculated using ICP and IOP together with geometric distances estimated from magnetic resonance imaging to adjust for hydrostatic effects.

    MAIN OUTCOME MEASURES: ICP, IOP, and TLCPD in different body positions.

    RESULTS: Between NTG patients and healthy volunteers, there were no differences in ICP, IOP, or TLCPD in supine, sitting, or HDT (P ≥ 0.11), except for IOP in HDT (P = 0.04). There was no correlation between visual field defect and TLCPD, IOP, or ICP and in any body position (P ≥ 0.39). Mean ICP in supine was 10.3 mmHg (SD = 2.7) in the NTG group (n = 13) and 11.3 (2.2) mmHg in the larger control group (n = 51) (P = 0.24).

    CONCLUSIONS: There was no evidence of reduced ICP in NTG patients as compared with healthy controls, either in supine or in upright position. Consequently, the hypothesis that NTG is caused by an elevated TLCPD from low ICP was not supported.

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  • 109.
    Lindén, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Östlund, Fanny
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Re: Linden et al.: Normal-tension glaucoma has normal intracranial pressure: a prospective study of intracranial pressure and intraocular pressure in different body positions (Ophthalmology. 2018;125:361-368) REPLY2018In: Ophthalmology, ISSN 0161-6420, E-ISSN 1549-4713, Vol. 125, no 6, p. e43-e44Article in journal (Refereed)
  • 110.
    Lindén, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Östlund, Fanny
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Re: Lindén et al.: Normal-tension glaucoma has normal intracranial pressure: a prospective study of intracranial pressure and intraocular pressure in different body positions (Ophthalmology.2018;125:361-368) REPLY2018In: Ophthalmology, ISSN 0161-6420, E-ISSN 1549-4713, Vol. 125, no 10, p. e74-e75Article in journal (Refereed)
  • 111.
    Luciano, Mark
    et al.
    Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
    Holubkov, Richard
    Adult Hydrocephalus Clinical Research Network, Department of Pediatrics, Division of Critical Care, University of Utah School of Medicine, Salt Lake City, Utah, USA; Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA.
    Williams, Michael A.
    Adult Hydrocephalus Clinical Research Network, Department of Pediatrics, Division of Critical Care, University of Utah School of Medicine, Salt Lake City, Utah, USA; Departments of Neurology and Neurological Surgery, University of Washington School of Medicine, Seattle, Washington, USA.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Nagel, Sean
    Adult Hydrocephalus Clinical Research Network, Department of Pediatrics, Division of Critical Care, University of Utah School of Medicine, Salt Lake City, Utah, USA; Center for Neurological Restoration, Cleveland Clinic, Cleveland, Ohio, USA; Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio, USA.
    Moghekar, Abhay
    Adult Hydrocephalus Clinical Research Network, Department of Pediatrics, Division of Critical Care, University of Utah School of Medicine, Salt Lake City, Utah, USA; Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Zwimpfer, Thomas
    Adult Hydrocephalus Clinical Research Network, Department of Pediatrics, Division of Critical Care, University of Utah School of Medicine, Salt Lake City, Utah, USA; Division of Neurosurgery, Department of Surgery, University of British Columbia, Vancouver, Canada.
    Katzen, Heather
    Adult Hydrocephalus Clinical Research Network, Department of Pediatrics, Division of Critical Care, University of Utah School of Medicine, Salt Lake City, Utah, USA; Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida, USA.
    Hanley, Daniel F.
    Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.
    Hamilton, Mark G.
    Adult Hydrocephalus Clinical Research Network, Department of Pediatrics, Division of Critical Care, University of Utah School of Medicine, Salt Lake City, Utah, USA; Division of Neurosurgery, Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Canada.
    Placebo-controlled effectiveness of idiopathic normal pressure hydrocephalus shunting: a randomized pilot trial2023In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 92, no 3, p. 481-489Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Multiple prospective nonrandomized studies have shown 60% to 70% of patients with idiopathic normal pressure hydrocephalus (iNPH) improve with shunt surgery, but multicenter placebo-controlled trial data are necessary to determine its effectiveness.

    OBJECTIVE: To evaluate the effectiveness of cerebrospinal fluid shunting in iNPH through comparison of open vs placebo shunting groups at 4 months using a pilot study.

    METHODS: Patients were randomized to a Codman Certas Plus valve (Integra LifeSciences) set at 4 (open shunt group) or 8 (“virtual off”; placebo group). Patients and assessors were blinded to treatment group. The primary outcome measure was 10-m gait velocity. Secondary outcome measures included functional scales for bladder control, activities of daily living, depression, and quality of life. Immediately after 4-month evaluation, all shunts were adjusted in a blinded fashion to an active setting and followed to 12 months after shunting.

    RESULTS: A total of 18 patients were randomized. At the 4-month evaluation, gait velocity increased by 0.28 ± 0.28 m/s in the open shunt group vs 0.04 ± 0.17 m/s in the placebo group. The estimated treatment difference was 0.22 m/s ([P = .071], 95% CI −0.02 to 0.46). Overactive Bladder Short Form symptom bother questionnaire significantly improved in open shunt vs placebo (P = .007). The 4-month treatment delay did not reduce the subsequent response to active shunting, nor did it increase the adverse advents rate at 12 months.

    CONCLUSION: This multicenter, randomized pilot study demonstrates the effectiveness, safety, and feasibility of a placebo-controlled trial in iNPH, and found a trend suggesting gait velocity improves more in the open shunt group than in the placebo group.

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  • 112.
    Lundkvist, B.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Malm, J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    An adjustable CSF shunt: advices for clinical use2003In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 108, no 1, p. 38-42Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The opening pressure and the resistance of a CSF shunt are essential for clinical use in order to set the proper opening pressure and to determine the shunt function in vivo. We find it of vital importance to validate and supplement the product description given by the manufacturer. The in vitro properties of a newly introduced, adjustable differential pressure valve with a siphon-preventing device (Strata valve) was compared with its predecessor (Delta valve).

    METHODS: An automated, computerized experimental set-up based on regulation of pressure, built into an incubator at 37 degrees C, was used. Opening pressure, resistance and siphon preventing properties were determined. Six brand-new shunts of each type with catheters were tested. The Delta valves were at a performance level of 1.5.

    RESULTS: The hydrodynamic properties of the Strata and Delta valves were similar. The anti-siphoning device was functioning for all valves. The estimated mean resistance for Delta and Strata shunts was 2.6 +/- 0.4 and 2.2 +/- 1.0 mmHg/ml/min, respectively. The mean opening pressure for the five performance levels of the Strata shunt are: 3.3, 5.1, 7.7, 10.7 and 13.1 mmHg. There may however, be considerable variations between the shunts.

    CONCLUSIONS: The Strata shunt is a properly working adjustable valve with anti-siphoning device that showed good reproducibility concerning opening pressure and resistance. At performance level 1.5, the new Strata shunt was similar to its predecessor concerning opening pressure and resistance. The given values of the different opening pressures and resistance could be used for in vivo testing of the valve function with a standard lumbar CSF infusion test.

  • 113. Lundkvist, B
    et al.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Kristensen, B
    Fagerlund, M
    Koskinen, L O
    Malm, J
    Cerebrospinal fluid hydrodynamics after placement of a shunt with an antisiphon device: a long-term study.2001In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 94, no 5, p. 750-6Article in journal (Refereed)
    Abstract [en]

    OBJECT: Few studies have been performed to investigate the cerebrospinal fluid (CSF) hydrodynamic profile in patients with idiopathic adult hydrocephalus syndrome (IAHS) before and after shunt implantation. The authors compared the in vivo CSF hydrodynamic properties, including the degree of gravity-induced CSF flow, of a shunt with an antisiphon device with a standard shunt.

    METHODS: Twelve patients with IAHS underwent insertion of shunts with Delta valves. Clinical testing, magnetic resonance imaging, and CSF hydrodynamic investigations were conducted with intracranial pressure (ICP), gravity effect, and pressure-flow curve of the shunt estimated at baseline and at 3 and 12 months postoperatively. No shunt was revised. Despite postoperative clinical improvement in all patients who received Delta valves, the mean ICP was only moderately reduced (mean decrease at 3 months 0.3 kPa [p = 0.02], at 12 months 0.2 kPa [not significant]). Patients with the greatest increase in ICP preoperatively had the most pronounced decrease postoperatively. The hydrostatic effect of the Delta valves was significantly lower than with the Hakim shunts (0.1-0.2 kPa compared with 0.6 kPa). The increased conductance (that is, lowered resistance) was up to 14 times higher with the Delta valves compared with preoperative levels.

    CONCLUSIONS: The function of a CSF shunt may be more complicated than previously thought; the subcutaneous pressure acting on the antisiphon device can modify the shunt characteristics. A compensatory increase in CSF production may counteract the increased outflow through the shunt. The improved CSF outflow conductance may increase the intracranial compliance and thereby dampen a pathological ICP waveform.

  • 114.
    Lundkvist, Bo
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Cerebrospinal fluid dynamics and long-term survival of the Strata(®) valve in idiopathic normal pressure hydrocephalus.2011In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 124, no 2, p. 115-121Article in journal (Refereed)
    Abstract [en]

    Objective -  Cerebrospinal fluid (CSF) dynamics and long-term shunt survival of the Strata(®) CSF shunt were evaluated in patients with idiopathic normal pressure hydrocephalus (INPH). Subjects and methods -  Seventy-two patients with INPH received a Strata(®) valve. A CSF infusion test, neuroimaging and video recording of gait were performed at baseline and at 6 months (n = 68) after surgery. Long-term shunt survivals were obtained from patient records. Results -  The shunt survival at 1 year was 94% and at 3 years 92.5%. Forty-nine patients (72%) had an improved gait. Two patients were improved despite non-functioning shunts, indicating a possible placebo response. Nineteen patients were not improved at the 6-month follow-up. The shunt tests revealed a functioning shunt in 12; thus, unnecessary shunt revisions could be avoided. Seventeen patients showed a siphoning effect. Shunt revisions were made in six patients. Eight hygromas/subdural hematomas were found. Conclusions -  The long-term survival of the Strata(®) valves was good, and a concern of complications is not a reason to exclude elderly with INPH from shunt surgery. Studies are needed to evaluate pros and cons of the anti-siphon device. Using a CSF shunt test, unnecessary shunt revisions may be avoided.

  • 115.
    Malm, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Birnefeld, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Zarrinkoob, Laleh
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Hemodynamic Disturbances in Posterior Circulation Stroke: 4D Flow Magnetic Resonance Imaging Added to Computed Tomography Angiography2021In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 15, article id 656769Article in journal (Refereed)
    Abstract [en]

    Objective: A clinically feasible, non-invasive method to quantify blood flow, hemodynamics, and collateral flow in the vertebrobasilar arterial tree is missing. The objective of this study was to evaluate the feasibility of quantifying blood flow and blood flow patterns using 4D flow magnetic resonance imaging (MRI) in consecutive patients after an ischemic stroke in the posterior circulation. We also explore if 4D-flow, analyzed in conjunction with computed tomography angiography (CTA), has potential as a diagnostic tool in posterior circulation stroke.

    Methods: Twenty-five patients (mean age 62 years; eight women) with acute ischemic stroke in the posterior circulation were investigated. At admission, all patients were examined with CTA followed by MRI (4D flow MRI and diffusion-weighted sequences) at median 4 days after the presenting event. Based on the classification of Caplan, patients were divided into proximal/middle (n = 16) and distal territory infarcts (n = 9). Absolute and relative blood flow rates were calculated for internal carotid arteries (ICA), vertebral arteries (VA), basilar artery (BA), posterior cerebral arteries (P1 and P2), and the posterior communicating arteries (Pcom). In a control group consisting of healthy elderly, the 90th and 10th percentiles of flow were calculated in order to define normal, increased, or decreased blood flow in each artery. “Major hemodynamic disturbance” was defined as low BA flow and either low P2 flow or high Pcom flow. Various minor hemodynamic disturbances were also defined. Blood flow rates were compared between groups. In addition, a comprehensive analysis of each patient’s blood flow profile was performed by assessing relative blood flow rates in each artery in conjunction with findings from CTA.

    Results: There was no difference in total cerebral blood flow between patients and controls [604 ± 117 ml/min vs. 587 ± 169 ml/min (mean ± SD), p = 0.39] or in total inflow to the posterior circulation (i.e., the sum of total VA and Pcom flows, 159 ± 63 ml/min vs. 164 ± 52 ml/min, p = 0.98). In individual arteries, there were no significant differences between patients and controls in absolute or relative flow. However, patients had larger interindividual relative flow variance in BA, P1, and P2 (p = 0.01, <0.01, and 0.02, respectively). Out of the 16 patients that had proximal/middle territory infarcts, nine had CTA findings in VA and/or BA generating five with major hemodynamic disturbance identified with 4D flow MRI. For those without CTA findings, seven had no or minor 4D flow MRI hemodynamic disturbance. Among nine patients with distal territory infarcts, one had major hemodynamic disturbances, while the remaining had minor disturbances.

    Conclusion: 4D flow MRI contributed to the identification of the patients who had major hemodynamic disturbances from the vascular pathologies revealed on CTA. We thus conclude that 4D flow MRI could add valuable hemodynamic information when used in conjunction with CTA.

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  • 116.
    Malm, Jan
    et al.
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Radiation Sciences.
    Idiopathic normal pressure hydrocephalus. Review2006In: Practical Neurology, Vol. 6, p. 14-27Article in journal (Refereed)
  • 117.
    Malm, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Jacobsson, Johan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Reference values for CSF outflow resistance and intracranial pressure in healthy elderly2011In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 76, no 10, p. 903-909Article in journal (Refereed)
    Abstract [en]

    This study reports reference values for ICP and R(out) and should be used for comparison when investigating disorders with suspected CSF dynamic disturbances in the elderly. ICP was in the same range as that reported in the young and middle-aged. The upper limit of R(out) was higher than previously believed to be the upper limit of normal for this age group.

  • 118.
    Malm, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Lundkvist, B
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Koskinen, L-O D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Kristensen, B
    CSF outflow resistance as predictor of shunt function. A long-term study2004In: Acta Neurol Scand, ISSN 0001-6314, Vol. 110, no 3, p. 154-160Article in journal (Refereed)
    Abstract
  • 119.
    Malm, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Cesarini, Kristina G
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Edsbagge, Mikael
    Institute of Neuroscience and Physiology, University of Gothenburg, Göteborg, Sweden.
    Kristensen, B
    Department of Neurology, Aalborg University, Aalborg, Denmark.
    Leijon, Göran
    Division of Neurology, Faculty of Health Sciences, University Hospital, Linköping, Sweden.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Implementation of a new CSF dynamic device: a multicenter feasibility study in 562 patients2012In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 125, no 3, p. 199-205Article in journal (Refereed)
    Abstract [en]

    Objectives: The cerebrospinal fluid (CSF) infusion test is frequently used when selecting hydrocephalus patients for shunt surgery. Very little has been reported regarding adverse events. We present a prospective feasibility study.

    Methods: Standardized devices for measuring CSF dynamics were built and 562 patients investigated: Needles were placed by lumbar puncture (LP). An automatic CSF infusion protocol was performed. Course of events during the investigation as well as adverse events were registered.

    Results: Preoperative evaluation of normal-pressure hydrocephalus was the most common indication (63%), followed by evaluation of shunt function (23%) and intracranial pressure recordings (14%). The LP was successfully performed in all but nine cases with 24 patients (4.3%) reporting major discomfort. Ringer infusion was performed in 474 investigations, and a valid measurement of the outflow resistance was received in 439 (93%). During the infusion phase, 17 (4%) patients reported severe headache. Infusion volume was significantly higher in patients having subjective symptoms during the infusion phase compared with those without adverse events. During 269 preoperative CSF tap tests, six (2%) patients had severe headache. Post-investigational headache was reported by 83 (15%) patients at the 24-h follow-up. No serious adverse events were observed.

    Conclusion: Infusion testing was safe and without serious adverse events with a high rate of successful procedures. The investigation was associated with expected mild to moderate discomfort.

  • 120.
    Manchester, Ian
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Andersson, K
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Shiriaev, Anton S
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Experimental Testing of a Method for On-Line Identification of the Cerebrospinal Fluid System2007In: 29th IEEE Annual International Conference on Engineering in Medicine and Biology, Lion, France, 2007, 2007, p. 2843-2846Conference paper (Refereed)
    Abstract
  • 121.
    Manchester, Ian
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Andersson, Kennet
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Andersson, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Shiriaev, Anton S
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    A nonlinear observer for on-line estimation of the cerebrospinal fluid outflow resistance.2008In: Automatica, ISSN 0005-1098, E-ISSN 1873-2836, Vol. 44, no 5, p. 1426-1430Article in journal (Refereed)
    Abstract [en]

    Accurate estimates of the outflow resistance of the human cerebrospinal fluid system are important for the diagnosis of a medical condition known as hydrocephalus. In this paper we design a nonlinear observer which provides on-line estimates of the outflow resistance, to the best of our knowledge the first method to do so. The output of the observer is proven to globally converge to an unbiased estimate. Its performance is experimentally verified using the same apparatus used to perform actual patient diagnoses and a specially-designed physical model of the human cerebrospinal fluid system.

  • 122.
    Manchester, Ian R
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Andersson, Kennet
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Andersson, Nina
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Shiriaev, Anton S
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    A nonlinear observer for on-line estimation of the cerebrospinal fluid outflow resistance2008In: Automatica, ISSN 0005-1098, E-ISSN 1873-2836, Vol. 44, p. 1426-1430Article in journal (Refereed)
  • 123. Marshall-Goebel, Karina
    et al.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Mulder, Edwin
    Gerlach, Darius
    Bershad, Eric
    Rittweger, Joern
    Effects of short-term exposure to head-down tilt on cerebral hemodynamics: a prospective evaluation of a spaceflight analog using phase-contrast MRI2016In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 120, no 12, p. 1466-1473Article in journal (Refereed)
    Abstract [en]

    Alterations in cerebral hemodynamics in microgravity are hypothesized to occur during spaceflight and could be linked to the Visual Impairment and Intracranial Pressure syndrome. Head-down tilt (HDT) is frequently used as a ground-based analog to simulate cephalad fluid shifts in microgravity; however, its effects on cerebral hemodynamics have not been well studied with MRI techniques. Here, we evaluate the effects of 1) various HDT angles on cerebral arterial and venous hemodynamics; and 2) exposure to 1% CO2 during an intermediate HDT angle (-12 degrees) as an additional space-related environmental factor. Blood flow, cross-sectional area (CSA), and blood flow velocity were measured with phase-contrast MRI in the internal jugular veins, as well as the vertebral and internal carotid arteries. Nine healthy male subjects were measured at baseline (supine, 0 degrees) and after 4.5 h of HDT at -6 degrees, -12 degrees (with and without 1% CO2), and -18 degrees. We found a decrease in total arterial blood flow from baseline during all angles of HDT. On the venous side, CSA increased with HDT, and outflow decreased during -12 degrees HDT (P = 0.039). Moreover, the addition of 1% CO2 to -12 degrees HDT caused an increase in total arterial blood flow (P = 0.016) and jugular venous outflow (P = 0.001) compared with -12 degrees HDT with ambient atmosphere. Overall, the results indicate decreased cerebral blood flow during HDT, which may have implications for microgravity-induced cerebral hemodynamic changes.

  • 124. Marshall-Goebel, Karina
    et al.
    Mulder, Edwin
    Bershad, Eric
    Laing, Charles
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stern, Claudia
    Rittweger, Jörn
    Intracranial and Intraocular Pressure During Various Degrees of Head-Down Tilt2017In: AEROSPACE MEDICINE AND HUMAN PERFORMANCE, ISSN 2375-6314, Vol. 88, no 1, p. 10-16Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: More than half of astronauts develop ophthalmic changes during long-duration spaceflight consistent with an abnormal intraocular and intracranial pressure (IOP, ICP) difference. The aim of our study was to assess IOP and ICP during head-down tilt (HDT) and the additive or attenuating effects of 1% CO2 and lower body negative pressure (LBNP). METHODS: In Experiment I, IOP and ICP were measured in nine healthy subjects after 3.5 h HDT in five conditions: -6 degrees, -12 degrees, and -18 degrees HDT, -12 degrees with 1% CO2, and -12 degrees with -20 mmHg LBNP. In Experiment II, IOP was measured in 16 healthy subjects after 5 min tilt at +12 degrees, 0 degrees, -6 degrees, -12 degrees, -18 degrees, and -24 degrees, with and without-40 mmHg LBNP. RESULTS: ICP was only found to increase from supine baseline during -18 degrees HDT (9.2 +/- 0.9 and 14.4 +/- 1 mmHg, respectively), whereas IOP increased from 15.7 +/- 0.3 mmHg at 0 degrees to 17.9 +/- 0.4 mmHg during -12 degrees HDT and from 15.3 +/- 0.4 mmHg at 0 degrees to 18.7 +/- 0.4 mmHg during-18 degrees HDT. The addition of -20 mmHg LBNP or 1% CO2 had no further effects on ICP or IOP. However, the use of -40 mmHg LBNP during HDT lowered IOP back to baseline values, except at 24 degrees HDT. DISCUSSION: A small, posterior intraocular-intracranial pressure difference (IOP > ICP) is maintained during HDT, and a sustained or further decreased difference may lead to structural changes in the eye in real and simulated microgravity.

  • 125.
    Mejtoft, Thomas
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Andersson, Britt M.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Pommer, Linda
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Karolina, Jonzén
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Kerstin, Ramser
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Lindahl, Olof A
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Kan en branschspecifik innovationsmodell öka ”success rate” för medicintekniska innovationer?2019Conference paper (Other academic)
  • 126.
    Mejtoft, Thomas
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Lindahl, Olof
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Öhberg, Fredrik
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Pommer, Linda
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Jonzén, Karolina
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Andersson, Britt M.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wåhlin, Anders
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Medtech innovation guide: an empiric model to support medical technology innovation2022In: Health and Technology, ISSN 2190-7188, E-ISSN 2190-7196, Vol. 12, no 5, p. 911-922Article in journal (Refereed)
    Abstract [en]

    Innovation has become increasingly important for most industries to cope with rapid technological changes as well as changing societal needs. Even though there are many sectors with specific needs when it comes to supporting innovation, the medical technology sector is facing several unique challenges that both increases the lead-time from idea to finished product and decreases the number of innovations that are developed. This paper presents a proposed innovation guide that has been developed and evaluated as a support for the innovation process within medical technology research. The guide takes the unique characteristics of the medical technology sector into account and serves as a usable guide for the innovator. The complete guide contains both a structure for the process and a usable web application to support the journey from idea to finished products and services. The paper also includes a new readiness level, Sect. 4.2 to provide support both when developing and determining the readiness for clinical implementation of a medical technology innovation.

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  • 127.
    Nilsson, Daniel
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Holmgren, Madelene
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Holmlund, Petter
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Dahlberg, Tobias
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Wiklund, Krister
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Andersson, Magnus
    Umeå University, Faculty of Science and Technology, Department of Physics. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Patient-specific brain arteries molded as a flexible phantom model using 3D printed water-soluble resin2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, article id 10172Article in journal (Refereed)
    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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  • 128.
    Podgoršak, Anthony
    et al.
    Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland.
    Trimmel, Nina Eva
    Division of Surgical Research, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
    Oertel, Markus Florian
    Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Arras, Margarete
    Division of Surgical Research, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Weisskopf, Miriam
    Division of Surgical Research, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
    Schmid Daners, Marianne
    Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland.
    Intercompartmental communication between the cerebrospinal and adjacent spaces during intrathecal infusions in an acute ovine in-vivo model2022In: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 19, no 1, article id 2Article in journal (Refereed)
    Abstract [en]

    Introduction: The treatment of hydrocephalus has been a topic of intense research ever since the first clinically successful use of a valved cerebrospinal fluid shunt 72 years ago. While ample studies elucidating different phenomena impacting this treatment exist, there are still gaps to be filled. Specifically, how intracranial, intrathecal, arterial, and venous pressures react and communicate with each other simultaneously.

    Methods: An in-vivo sheep trial (n = 6) was conducted to evaluate and quantify the communication existing within the cranio-spinal, arterial, and venous systems (1 kHz sampling frequency). Standardized intrathecal infusion testing was performed using an automated infusion apparatus, including bolus and constant pressure infusions. Bolus infusions entailed six lumbar intrathecal infusions of 2 mL Ringer’s solution. Constant pressure infusions were comprised of six regulated pressure steps of 3.75 mmHg for periods of 7 min each. Mean pressure reactions, pulse amplitude reactions, and outflow resistance were calculated.

    Results: All sheep showed intracranial pressure reactions to acute increases of intrathecal pressure, with four of six sheep showing clear cranio-spinal communication. During bolus infusions, the increases of mean pressure for intrathecal, intracranial, arterial, and venous pressure were 16.6 ± 0.9, 15.4 ± 0.8, 3.9 ± 0.8, and 0.1 ± 0.2 mmHg with corresponding pulse amplitude increases of 2.4 ± 0.3, 1.3 ± 0.3, 1.3 ± 0.3, and 0.2 ± 0.1 mmHg, respectively. During constant pressure infusions, mean increases from baseline were 14.6 ± 3.8, 15.5 ± 4.2, 4.2 ± 8.2, and 3.2 ± 2.4 mmHg with the corresponding pulse amplitude increases of 2.5 ± 3.6, 2.5 ± 3.0, 7.7 ± 4.3, and 0.7 ± 2.0 mmHg for intrathecal, intracranial, arterial, and venous pulse amplitude, respectively. Outflow resistances were calculated as 51.6 ± 7.8 and 77.8 ± 14.5 mmHg/mL/min for the bolus and constant pressure infusion methods, respectively—showing deviations between the two estimation methods.

    Conclusions: Standardized infusion tests with multi-compartmental pressure recordings in sheep have helped capture distinct reactions between the intrathecal, intracranial, arterial, and venous systems. Volumetric pressure changes in the intrathecal space have been shown to propagate to the intraventricular and arterial systems in our sample, and to the venous side in individual cases. These results represent an important step into achieving a more complete quantitative understanding of how an acute rise in intrathecal pressure can propagate and influence other systems.

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  • 129.
    Qvarlander, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Jacobsson, Johan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Cerebrospinal fluid and blood flow patterns in idiopathic normal pressure hydrocephalus2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 135, no 5, p. 576-584Article in journal (Refereed)
    Abstract [en]

    Objectives: Increased aqueduct cerebrospinal fluid (CSF) flow pulsatility and, recently, a reversed CSF flow in the aqueduct have been suggested as hallmarks of idiopathic normal pressure hydrocephalus (INPH). However, these findings have not been adequately confirmed. Our objective was to investigate the flow of blood and CSF in INPH, as compared to healthy elderly, in order to clarify which flow parameters are related to the INPH pathophysiology.

    Materials and Methods: Sixteen INPH patients (73 years) and 35 healthy subjects (72 years) underwent phase-contrast magnetic resonance imaging (MRI). Measurements included aqueduct and cervical CSF flow, total arterial inflow (tCBF; i.e. carotid + vertebral arteries), and internal jugular vein flow. Flow pulsatility, net flow, and flow delays were compared (multiple linear regression, correcting for sex and age).

    Results: Aqueduct stroke volume was higher in INPH than healthy (148±95 vs 90±50 mL, P<.05). Net aqueduct CSF flow was similar in magnitude and direction. The cervical CSF stroke volume was lower (P<.05). The internal carotid artery net flow was lower in INPH (P<.05), although tCBF was not. No differences were found in internal jugular vein flow or flow delays.

    Conclusions: The typical flow of blood and CSF in INPH was mainly characterized by increased CSF pulsatility in the aqueduct and reduced cervical CSF pulsatility. The direction of mean net aqueduct CSF flow was from the third to the fourth ventricle. Our findings may reflect the altered distribution of intracranial CSF volume in INPH, although the causality of these relationships is unclear.

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  • 130.
    Qvarlander, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jacobsson, Johan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Differences in cerebral blood flow and CSF flow between INPH and healthy elderlyManuscript (preprint) (Other academic)
    Abstract [en]

    Idiopathic normal pressure hydrocephalus (INPH) is linked to disturbance of the CSF circulation, though the exact nature of the disturbance is not clarified. Phase contrast magnetic resonance imaging (PC-MRI) allows for measurement of local CSF and blood flows, and has been applied in hydrocephalus to demonstrate changes in both cerebral blood flow and aqueduct CSF flow. Many of these studies have, however been based on small numbers of subjects, or poorly defined selection criteria. This study therefore aimed to confirm if cerebral blood flow and CSF flow between compartments differed between INPH subjects and healthy elderly.

    Forty-three healthy elderly and 22 patients diagnosed with INPH according to the INPH guidelines were investigated with PC-MRI measurements of cerebral arterial inflow (CBF) and internal jugular venous outflow, cervical CSF flow, and aqueduct CSF flow. Both net flows, pulsatile aspects of flow, and delays between flow waveforms were analysed.

    Pulsatility in the aqueduct flow was significantly higher in INPH than healthy elderly (aqueduct stroke volume: 189±184 vs. 86±46 ml, p<0.01). There was larger variation in aqueduct net flow in INPH (SD: 1.31 vs. 0.25 ml/min), but the mean net flow did not differ. Cerebral blood flow and internal jugular vein flow showed no significant differences between the groups, though there was a trend toward lower CBF in the diastolic phase and higher CBF pulsatility index. No differences were found in flow delays.

    In conclusion, cerebral in- and outflow of blood, and cervical CSF flow were similar in healthy elderly and INPH subjects. Aqueduct flow showed higher pulsatility in INPH, but there was no general reversal of the direction of aqueduct net flow. 

  • 131.
    Qvarlander, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Lundkvist, Bo
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Pulsatility in CSF dynamics: pathophysiology of idiopathic normal pressure hydrocephalus2013In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 84, no 7, p. 735-741Article in journal (Refereed)
    Abstract [en]

    Background: It is suggested that disturbed CSF dynamics are involved in the pathophysiology of idiopathic normal pressure hydrocephalus (INPH). The pulsatility curve describes the relationship between intracranial pressure (ICP) and the amplitude of cardiac related ICP pulsations. The position of baseline ICP on the curve provides information about the physiological state of the CSF dynamic system. The objective of the study was to investigate if shunt surgery modifies the pulsatility curve and the baseline position on the curve, and how this relates to gait improvement in INPH.

    Methods: 51 INPH patients were investigated with lumbar CSF dynamic investigations preoperatively and 5 months after shunt surgery. During the investigation, ICP was measured at baseline, and then a CSF sample was removed, resulting in pressure reduction. After this, ICP was regulated with an automated infusion protocol, with a maximum increase of 24 mm Hg above baseline. The pulsatility curve was thus determined in a wide range of ICP values. Gait improvement was defined as a gait speed increase >= 0.1 m/s.

    Results: The pulsatility curve was unaltered by shunting. Baseline ICP and amplitude were reduced (-3.0 +/- 2.9 mm Hg; -1.1 +/- 1.5 mm Hg; p < 0.05, n = 51). Amplitude reduction was larger for gait improvers (-1.2 +/- 1.6 mm Hg, n = 42) than non-improvers (-0.2 +/- 0.5 mm Hg, n = 9) (p < 0.05) although mean ICP reduction did not differ.

    Conclusions: The pulsatility curve was not modified by shunt surgery, while the baseline position was shifted along the curve. Observed differences between gait improvers and non-improvers support cardiac related ICP pulsations as a component of INPH pathophysiology.

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  • 132.
    Qvarlander, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    CSF dynamic analysis of a predictive pulsatility-based infusion test for normal pressure hydrocephalus2014In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 52, no 1, p. 75-85Article in journal (Refereed)
    Abstract [en]

    Disturbed cerebrospinal fluid (CSF) dynamics are part of the pathophysiology of normal pressure hydrocephalus (NPH) and can be modified and treated with shunt surgery. This study investigated the contribution of established CSF dynamic parameters to AMPmean, a prognostic variable defined as mean amplitude of cardiac-related intracranial pressure pulsations during 10 min of lumbar constant infusion, with the aim of clarifying the physiological interpretation of the variable. AMPmean and CSF dynamic parameters were determined from infusion tests performed on 18 patients with suspected NPH. Using a mathematical model of CSF dynamics, an expression for AMPmean was derived and the influence of the different parameters was assessed. There was high correlation between modelled and measured AMPmean (r = 0.98, p < 0.01). Outflow resistance and three parameters relating to compliance were identified from the model. Correlation analysis of patient data confirmed the effect of the parameters on AMPmean (Spearman's ρ = 0.58-0.88, p < 0.05). Simulated variations of ±1 standard deviation (SD) of the parameters resulted in AMPmean changes of 0.6-2.9 SD, with the elastance coefficient showing the strongest influence. Parameters relating to compliance showed the largest contribution to AMPmean, which supports the importance of the compliance aspect of CSF dynamics for the understanding of the pathophysiology of NPH.

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  • 133.
    Qvarlander, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    The pulsatility curve: the relationship between mean intracranial pressure and pulsation amplitude2010In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 31, no 11, p. 1517-1528Article in journal (Refereed)
    Abstract [en]

    The amplitude of cardiac-related pulsations in intracranial pressure has recently been suggested as useful for selecting patients for shunt surgery in hydrocephalus. To better understand how shunting affects these pulsations, we aim to model the relationship between mean pressure and pulsation amplitude in a wide range, including low pressures typically found after shunt surgery. Twenty-five patients with probable idiopathic normal pressure hydrocephalus were examined with lumbar constant pressure infusion investigations including drainage of cerebrospinal fluid. Mean pressure and pulsation amplitude were determined for consecutive 1.5 s intervals, starting at peak pressure (ca 35 mmHg), after infusion, continuing during spontaneous return to baseline and drainage to 0 mmHg. The amplitude versus pressure relationship revealed a linear phase at higher pressures (14-32 mmHg, lack of fit test: p = 0.79), a transitional phase and an essentially constant phase at low pressures (0-10 mmHg, slope = -0.02, lack of fit test: p = 0.88). Individual patients' baseline values were found in all three phases. The model and methodology presented in this paper can be used to preoperatively identify patients with potential for postoperative amplitude decrease and to predict how much the amplitude can be reduced.

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  • 134.
    Qvarlander, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Sundström, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Postural effects on intracranial pressure: modeling and clinical evaluation2013In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, no 10, p. 1474-1480Article in journal (Refereed)
    Abstract [en]

    Introduction The physiological effect of posture on intracranial pressure (ICP) is not well described. This study defined and evaluated three mathematical models describing the postural effects on ICP, designed to predict ICP at different head-up tilt-angles from the supine ICP value.

    Methods Model I was based on a hydrostatic indifference point for the cerebrospinal fluid (CSF) system, i.e. the existence of a point in the system where pressure is independent of body position. Models II and III were based on Davson's equation for CSF absorption, which relates ICP to venous pressure, and postulated that gravitational effects within the venous system are transferred to the CSF system. Model II assumed a fully communicating venous system and model III that collapse of the jugular veins at higher tilt-angles creates two separate hydrostatic compartments. Evaluation of the models was based on ICP measurements at seven tilt-angles (0-71°)in 27 normal pressure hydrocephalus patients.

    Results ICP decreased with tilt-angle (ANOVA, p<0.01). The reduction was well predicted by model III (ANOVA lack-of-fit: p=0.65), which showed excellent fit against measured ICP. Neither model I nor II adequately described the reduction in ICP (ANOVA lack-of-fit: p<0.01).

    Conclusion Postural changes in ICP could not be predicted based on the currently accepted theory of a hydrostatic indifference point for the CSF system, but a new model combining Davson's equation for CSF absorption and hydrostatic gradients in a collapsible venous system performed well and can be useful in future research on gravity and CSF physiology.

  • 135.
    Ren, Keni
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Karlsson, Johannes
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Identifying Individual Bears in a Zoo Setting Using Visual Biometrics and Behaviour InformationManuscript (preprint) (Other academic)
  • 136. Ryska, Pavel
    et al.
    Slezak, Ondrej
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Zizka, Jan
    Radiological markers of idiopathic normal pressure hydrocephalus: Relative comparison of their diagnostic performance2020In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 408, article id 116581Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Numerous radiological measures have been proposed as imaging biomarkers of idiopathic normal pressure hydrocephalus (iNPH), however, the number of studies systematically comparing their diagnostic values remains limited. The study objective was to compare the diagnostic performance of fifteen cross-sectional imaging iNPH biomarkers.

    MATERIALS AND METHODS: Eighty subjects were prospectively enrolled in the study: 35 subjects with clinically confirmed iNPH and 45 matched healthy controls (HC). Values of linear, angular and index measurements including three newly proposed biomarkers were obtained from 3T brain MRI studies by two independent readers. Diagnostic performance of biomarkers was studied by using receiver operating characteristic (ROC) analysis and t-statistic.

    RESULTS: All biomarkers studied were able to reliably differentiate iNPH subjects from HC (p < .001) except for cella media-to-temporal horn ratio. Z-Evans index, vertical cella media and vertical frontal horn diameters showed the highest discriminatory power between iNPH and HC groups (area under curve >0.99). Simple linear measurements of vertical (0.99) or horizontal (0.95) frontal horn diameters showed results comparable to calculated ratios, i.e. z-Evans (0.99) and Evans (0.96) indexes, respectively.

    CONCLUSION: The best diagnostic performance among fifteen radiological iNPH biomarkers was found in linear measurements referring to caudocranial alterations of the ventricular geometry, outweighing those referring to laterolateral ventricular enlargement (as e.g. commonly used Evans index). Simple linear measurements of vertical or horizontal frontal horn diameters showed comparable results to calculated, more time-consuming z-Evans or Evans indexes, respectively.

  • 137.
    Sandvig, Axel
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
    Arnell, Kai
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Analysis of Codman microcerebrospinal fluid shunt2018In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 8, no 10, article id e01002Article in journal (Refereed)
    Abstract [en]

    Introduction: Ventriculo-peritoneal cerebrospinal fluid (CSF) shunt is the most common method of treating pediatric hydrocephalus. The Codman microadjustable valve (CMAV) is a CSF shunt constructed for children. The objective of the study was (a) to analyze complications after insertion of a CMAV shunt in hydrocephalic children, (b)to analyze complications after replacing a CMAV by an adult-type Codman Hakim adjustable valve shunt (CHAV), and to (c) analyze the in vitro characteristics of the CMAV shunt and correlate the findings with the clinical performance of the shunt.

    Methods: A retrospective study analyzed a cohort of hydrocephalic children who had received a CMAV shunt and later replaced by a CHAV shunt. We report on the complications that resulted from replacing the CMAV with the CHAV. We tested six CMAV shunts with or without an antisiphon device (ASD) in which opening pressure, resistance, sensitivity to abdominal pressure, ASD position dependency, and function were determined. The test results were correlated with the clinical performance of the shunt in the retrospective study.

    Results: Thirty-seven children (19 boys, 18 girls) were identified. Within the first month after shunt placement, a total of 10 patients (27%) developed complications including infections, hygromas, and shunt dysfunction. Shunt survival varied from 1week to 145 months. Over the 10-year follow-up period, 13 children had their shunts replaced, six of them with a CHAV without any further complications. A bench test of the CMAV was done to test whether the opening pressure was in agreement with the manufacturer's specifications. Our results were generally in agreement with specifications stated by the manufacturer.

    Conclusion: Replacing a CMAV with a CHAV was well tolerated by the patients. Bench test results were generally in agreement with manufacturers specifications. Replacing a CMAV with a CHAV in pediatric hydrocephalus patients can be accomplished safely.

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  • 138.
    Schrauben, Eric
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Wisconsin, USA.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Department of Radiology, University of Wisconsin – Madison, Madison, Wisconsin, USA.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Spaak, Erik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wieben, Oliver
    University of Wisconsin – Madison, Madison, Wisconsin, USA.
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Fast 4D flow MRI intracranial segmentation and quantification in tortuous arteries2015In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 42, no 5, p. 1458-1464Article in journal (Refereed)
    Abstract [en]

    PurposeTo describe, validate, and implement a centerline processing scheme (CPS) for semiautomated segmentation and quantification in carotid siphons of healthy subjects. 4D flow MRI enables blood flow measurement in all major cerebral arteries with one scan. Clinical translational hurdles are time demanding postprocessing and user-dependence induced variability during analysis. Materials and MethodsA CPS for 4D flow data was developed to automatically separate cerebral artery trees. Flow parameters were quantified at planes along the centerline oriented perpendicular to the vessel path. At 3T, validation against 2D phase-contrast (PC) magnetic resonance imaging (MRI) and 4D flow manual processing was performed on an intracranial flow phantom for constant flow, while pulsatile flow validation was performed in the internal carotid artery (ICA) of 10 healthy volunteers. The CPS and 4D manual processing times were measured and compared. Flow and area measurements were also demonstrated along the length of the ICA siphon. ResultsPhantom measurements for area and flow were highly correlated between the CPS and 2D measurements (area: R=0.95, flow: R=0.94), while in vivo waveforms were highly correlated (R=0.93). Processing time was reduced by a factor of 4.6 compared with manual processing. Whole ICA measurements revealed a significantly decreased area in the most distal segment of the carotid siphon (P=0.0017), with flow unchanged (P=0.84). ConclusionThis study exhibits fast semiautomated analysis of intracranial 4D flow MRI. Internal consistency was shown through flow conservation along the tortuous ICA siphon, which is typically difficult to assess. J. Magn. Reson. Imaging 2015;42:1458-1464.

  • 139. Stephensen, H
    et al.
    Andersson, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Tisell, M
    Wikkelsö, C
    Objective B wave analysis in 55 patients with non-communicating and communicating hydrocephalus2005In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 76, p. 965-970Article in journal (Refereed)
    Abstract [en]

    Background: B waves, slow and rhythmic oscillations in intracranial pressure (ICP), are claimed to be one of the best predictors of outcome after surgery for normal pressure hydrocephalus (NPH).

    Object: To determine the relation between the percentage of B waves and outcome in patients with hydrocephalus, and also the diurnal variation of B waves.

    Methods: ICP and patient behaviour were recorded overnight (17 to 26 hours) in 29 patients with non-communicating hydrocephalus and 26 with NPH. The B wave activity, measured with an amplitude threshold of 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, and 5.0 mm Hg, was estimated as the percentage of total monitoring time (% B waves) using a computer algorithm, and correlated with postoperative outcome, defined as changes in 12 standardised symptoms and signs.

    Results: There was no linear correlation between improvement after surgery in the 55 patients and total % B waves, but a correlation was found between improvement and % B waves during sleep (r = 0.39, p = 0.04). The percentage of B waves was the same during sleep and wakefulness, and patients with NPH had the same proportion of B waves as the non-communicating patients.

    Conclusions: B waves are commonly observed in patients with both communicating and non-communicating hydrocephalus, but are only weakly related to the degree of postsurgical improvement.

  • 140.
    Sundström, Nina
    et al.
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Andersson, Kennet
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Marmarou, Anthony
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Comparison between 3 infusion methods to measure cerebrospinal fluid outflow conductance2010In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 113, no 6, p. 1294-1303Article in journal (Refereed)
    Abstract [en]

    Object There are several infusion methods available to estimate the outflow conductance (Cout) or outflow resistance (Rout = 1/Cout) of the CSF system. It has been stated that for unknown reasons, the bolus infusion method estimates a higher Cout than steady-state infusion methods. The aim of this study was to compare different infusion methods for estimation of Cout.

    Methods The following 3 different infusion methods were used: the bolus infusion method (Cout bol); the constant flow infusion method, both static (Cout stat) and dynamic (Cout dyn) analyses; and the constant pressure infusion method (Cout cpi). Repeated investigations were performed on an experimental model with well-known characteristics, with and without physiological pressure variations (B-waves, breathing, and so on). All 3 methods were also performed in a randomized order during the same investigation in 20 patients with probable or possible idiopathic normal-pressure hydrocephalus; 6 of these patients had a shunt and 14 did not.

    Results Without the presence of physiological pressure variations, the concordance in the experimental model was good between all methods. When they were added, the repeatability was better for the steady-state methods and a significantly higher Cout was found with the bolus method in the region of clinically relevant Cout (p < 0.05). The visual fit for the bolus infusion was dependent on subjective assessment by the operator. This experimental finding was confirmed by the clinical results, where significant differences were found in the investigations in patients without shunts between Cout of the visual bolus method and Cout stat, Cout dyn, and Cout cpi (4.58, 4.18, and 6.12 μl/[second × kPa], respectively).

    Conclusions This study emphasized the necessity for standardization of Cout measurements. An experienced operator could partly compensate for difficulties in correctly estimating the pressure parameters for the bolus infusion method, but for the general user this study suggests a steady-state method for estimating Cout.

  • 141.
    Sundström, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lagebrant, Marcus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Subdural hematomas in 1846 patients with shunted idiopathic normal pressure hydrocephalus: treatment and long-term survival2018In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 129, no 3, p. 797-804Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Subdural hematoma (SDH) is the most common serious adverse event in patients with shunts. Adjustable shunts are used with increasing frequency and make it possible to noninvasively treat postoperative SDH. The objective of this study was to describe the prevalence and treatment preferences of SDHs, based on fixed or adjustable shunt valves, in a national cohort of patients with shunted idiopathic normal pressure hydrocephalus (iNPH), as well as to evaluate the effect of SDH and treatment on long-term survival.

    METHODS Patients with iNPH who received a CSF shunt in Sweden from 2004 to 2015 were included in a prospective quality registry (n = 1846) and followed regarding SDH, its treatment, and mortality. The treatment of SDH was categorized into surgery, opening pressure adjustments, or no treatment.

    RESULTS During the study period, the proportion of adjustable shunts increased from 75% to 95%. Ten percent (n = 184) of the patients developed an SDH. In 103 patients, treatment was solely opening pressure adjustment. Surgical treatment was used in 66 cases (36%), and 15 (8%) received no treatment. In patients with fixed shunt valves, 90% (n = 17) of SDHs were treated surgically compared with 30% (n = 49) in patients with adjustable shunts (p < 0.001). There was no difference in long-term patient survival between the SDH and non-SDH groups or between different treatments.

    CONCLUSIONS SDH remains a common complication after shunt surgery, but adjustable shunts reduced the need for surgical interventions. SDH and treatment did not significantly affect survival in this patient group, thus the noninvasive treatment offered by adjustable shunts considerably reduces the level of severity for this common adverse event.

  • 142.
    Sundström, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Venous and cerebrospinal fluid flow in multiple sclerosis. A case-control study.2010In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 68, no 2, p. 255-259Article in journal (Refereed)
    Abstract [en]

    The prevailing view on multiple sclerosis etiopathogenesis has been challenged by the suggested new entity chronic cerebrospinal venous insufficiency. To test this hypothesis, we studied 21 relapsing-remitting multiple sclerosis cases and 20 healthy controls with phase-contrast magnetic resonance imaging. In addition, in multiple sclerosis cases we performed contrast-enhanced magnetic resonance angiography. We found no differences regarding internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux. Three of 21 cases had internal jugular vein stenoses. In conclusion, we found no evidence confirming the suggested vascular multiple sclerosis hypothesis.

  • 143.
    Vikner, Tomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Karalija, Nina
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Lindenberger, Ulman
    Bäckman, Lars
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Cerebral arterial pulsatility is linked to hippocampal microvascular function and episodic memory in healthy older adults2021In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 41, no 7, p. 1778-1790Article in journal (Refereed)
    Abstract [en]

    Microvascular damage in the hippocampus is emerging as a central cause of cognitive decline and dementia in aging. This could be a consequence of age-related decreases in vascular elasticity, exposing hippocampal capillaries to excessive cardiac-related pulsatile flow that disrupts the blood-brain barrier and the neurovascular unit. Previous studies have found altered intracranial hemodynamics in cognitive impairment and dementia, as well as negative associations between pulsatility and hippocampal volume. However, evidence linking features of the cerebral arterial flow waveform to hippocampal function is lacking. We used a high-resolution 4D flow MRI approach to estimate global representations of the time-resolved flow waveform in distal cortical arteries and in proximal arteries feeding the brain in healthy older adults. Waveform-based clustering revealed a group of individuals featuring steep systolic onset and high amplitude that had poorer hippocampus-sensitive episodic memory (p = 0.003), lower whole-brain perfusion (p = 0.001), and weaker microvascular low-frequency oscillations in the hippocampus (p = 0.035) and parahippocampal gyrus (p = 0.005), potentially indicating compromised neurovascular unit integrity. Our findings suggest that aberrant hemodynamic forces contribute to cerebral microvascular and hippocampal dysfunction in aging.

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  • 144.
    Vikner, Tomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Björnfot, Cecilia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Blood-brain barrier permeability, vascular density, and cerebral 4D flow MRI hemodynamics in a population-based elderly cohortManuscript (preprint) (Other academic)
  • 145.
    Vikner, Tomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karalija, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Lundquist, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Gallewicz, Nikodemus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Dahlin, Magnus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindenberger, Ulman
    Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Max Planck, UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany; Max Planck, UCL Centre for Computational Psychiatry and Ageing Research, London, United Kingdom.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Bäckman, Lars
    Ageing Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    5-year associations among cerebral arterial pulsatility, perivascular space dilation, and white matter lesions2022In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 92, no 5, p. 871-881Article in journal (Refereed)
    Abstract [en]

    Objective: High cerebral arterial pulsatility index (PI), white matter lesions (WMLs), enlarged perivascular spaces (PVSs), and lacunar infarcts are common findings in the elderly population, and considered indicators of small vessel disease (SVD). Here, we investigate the potential temporal ordering among these variables, with emphasis on determining whether high PI is an early or delayed manifestation of SVD.

    Methods: In a population-based cohort, 4D flow MRI data for cerebral arterial pulsatility was collected for 159 participants at baseline (age 64–68), and for 122 participants at follow-up 5 years later. Structural MRI was used for WML and PVS segmentation, and lacune identification. Linear mixed-effects (LME) models were used to model longitudinal changes testing for pairwise associations, and latent change score (LCS) models to model multiple relationships among variables simultaneously.

    Results: Longitudinal 5-year increases were found for WML, PVS, and PI. Cerebral arterial PI at baseline did not predict changes in WML or PVS volume. However, WML and PVS volume at baseline predicted 5-year increases in PI. This was shown for PI increases in relation to baseline WML and PVS volumes using LME models (R (Formula presented.) 0.24; p < 0.02 and R (Formula presented.) 0.23; p < 0.03, respectively) and LCS models ((Formula presented.) = 0.28; p = 0.015 and (Formula presented.) = 0.28; p = 0.009, respectively). Lacunes at baseline were unrelated to PI.

    Interpretation: In healthy older adults, indicators of SVD are related in a lead–lag fashion, in which the expression of WML and PVS precedes increases in cerebral arterial PI. Hence, we propose that elevated PI is a relatively late manifestation, rather than a risk factor, for cerebral SVD. 

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  • 146.
    Vikner, Tomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Holmgren, Madelene
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Characterizing pulsatility in distal cerebral arteries using 4D flow MRI2020In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 40, no 12, p. 2429-2440Article in journal (Refereed)
    Abstract [en]

    Recent reports have suggested that age-related arterial stiffening and excessive cerebral arterial pulsatility cause blood-brain barrier breakdown, brain atrophy and cognitive decline. This has spurred interest in developing non-invasive methods to measure pulsatility in distal vessels, closer to the cerebral microcirculation. Here, we report a method based on four-dimensional (4D) flow MRI to estimate a global composite flow waveform of distal cerebral arteries. The method is based on finding and sampling arterial waveforms from thousands of cross sections in numerous small vessels of the brain, originating from cerebral cortical arteries. We demonstrate agreement with internal and external reference methods and show the ability to capture significant increases in distal cerebral arterial pulsatility as a function of age. The proposed approach can be used to advance our understanding regarding excessive arterial pulsatility as a potential trigger of cognitive decline and dementia.

  • 147. Vinje, Vegard
    et al.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Mardal, Kent-Andre
    Rognes, Marie E.
    Stoverud, Karen-Helene
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Intracranial pressure elevation alters CSF clearance pathways2020In: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 17, no 1, article id 29Article in journal (Refereed)
    Abstract [en]

    Background: Infusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Here, we investigate to what extent the proposed glymphatic or paravascular pathway (or similar pathways) modifies the results of the traditional mathematical models.

    Methods: We used a compartment model to estimate pressure in the subarachnoid space and the paravascular spaces. For the arachnoid granulations, the cribriform plate and the glymphatic circulation, resistances were calculated and used to estimate pressure and flow before and during an infusion test. Finally, different variations to the model were tested to evaluate the sensitivity of selected parameters.

    Results: At baseline intracranial pressure (ICP), we found a very small paravascular flow directed into the subarachnoid space, while 60% of the fluid left through the arachnoid granulations and 40% left through the cribriform plate. However, during the infusion, 80% of the fluid left through the arachnoid granulations, 20% through the cribriform plate and flow in the PVS was stagnant. Resistance through the glymphatic system was computed to be 2.73 mmHg/(mL/min), considerably lower than other fluid pathways, giving non-realistic ICP during infusion if combined with a lymphatic drainage route.

    Conclusions: The relative distribution of CSF flow to different clearance pathways depends on ICP, with the arachnoid granulations as the main contributor to outflow. As such, ICP increase is an important factor that should be addressed when determining the pathways of injected substances in the subarachnoid space. Our results suggest that the glymphatic resistance is too high to allow for pressure driven flow by arterial pulsations and at the same time too small to allow for a direct drainage route from PVS to cervical lymphatics.

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  • 148.
    Wahlin, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Holmlund, Petter
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Fellows, Abigail M.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Buckey, Jay C.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Re: Wahlin et al.: Optic nerve length before and after spaceflight [REPLY]2021In: Ophthalmology, ISSN 0161-6420, E-ISSN 1549-4713, Vol. 128, no 5, p. E28-E28Article in journal (Other academic)
  • 149. Wang, L
    et al.
    el Azazi, M
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lillemor, W
    Background light adaptation of the retinal neuronal adaptive system. I. Effect of background light intensity.2001In: Documenta Ophthalmologica, ISSN 0012-4486, E-ISSN 1573-2622, Vol. 103, no 1, p. 13-26Article in journal (Refereed)
    Abstract [en]

    The behaviour of the neuronal adaptive retinal mechanisms to environmental light exposures was studied by measuring the oscillatory potentials (OPs) of the electroretinogram. Dark adapted rats were exposed to four levels of background light (BG), starting at a 'low scotopic' level of 1.43x 10(6) cd/m2, increased by steps of two log units, through 'high scotopic' -, 'low mesopic' - and finally the 'high mesopic' BG of 1.43x 10(0) cd/m2. The summed oscillatory response significantly increased as the BG intensity was raised, except at the 'high mesopic' level. The amplitudes of the a- and b-waves reduced as the BG light increased above the 'high scotopic' level. Each OP responded individually to the different BGs. O1 and O2, significantly enhanced at the 'low scotopic' BG. The amplitudes of the three later OPs increased significantly at the 'low mesopic' BG. The adaptational behaviour of the retinal oscillatory response to BG illumination was different to that of the a- and b- waves. The results indicate that the adaptational neuronal system, as reflected by the OPs, seems to be relatively robust and is separate from the slower photochemical adaptive process in the distal retina. The tentative corollary suggests the oscillatory system to play a vision-preserving role, possibly as an alert against undue depletion of the slowly regenerating visual pigment. The enhancement of the oscillatory response at the 'mesopic' illumination levels indicate both scotopic and photopic processes to contribute to neuronal adaptive activity of the retina.

  • 150.
    Wang, Ling
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Department of Ophthalmology, Ruijin Hospital, Medicine School of Shanghai, Jiaotong University, Shanghai, China.
    el Azazi, Mildred
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Burstedt, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Wachtmeister, Lillemor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The response of the neuronal adaptive system to background illumination and readaptation to dark in the immature retina2015In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 93, no 2, p. 146-153Article in journal (Refereed)
    Abstract [en]

    Purpose: Developmental characteristics of the neuronal adaptive system of the retina, focusing on background light (BGL) adaptation and readaptation functions, were studied by measuring the oscillatory response (SOP) of the electroretinogram (ERG).

    Methods: Digitally filtered and conventional ERGs were simultaneously recorded. Rats aged 15 and 17 days were studied during exposure to BGLs of two mesopic intensities and during readaptation to dark.

    Results: Results were compared to adult rats. In ‘low mesopic’ BGL SOP instantly dropped significantly to about half of its dark-adapted (DA) value contrary to mature rats, in which the SOP significantly increased. In ‘high mesopic’ BGL SOP decreased to about 20% and 30% of DA values in immature and adult rats, respectively. The process of recovery of SOP in darkness lacked the transient enhancement immediately as BGL was turned off, characteristic of adult rats. There were no major age differences in adaptive behaviour of a-wave. In young rats, recovery of b-wave was relatively slower.

    Conclusions: Properties of BGL adaptation and readaptation functions of the neuronal adaptive system in baby retina differed compared to the adult one by being less forceful and more restrained. Handling of mesopic illumination and recovery in the dark was immature. Development of these functions of the neuronal adaptive system progresses postnatally and lags behind that of the photoreceptor response and seems to be delayed also compared to that of the bipolar response.

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