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  • 1.
    Ambarki, Khalid
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Zarrinkoob, Laleh
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    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).
    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 Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Blood flow of ophthalmic artery in healthy individuals determined by phase-contrast magnetic resonance imaging2013In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 54, no 4, p. 2738-2745Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Recent development of magnetic resonance imaging (MRI) offers new possibilities to assess ocular blood flow. This prospective study evaluates the feasibility of phase-contrast MRI (PCMRI) to measure flow rate in the ophthalmic artery (OA) and establish reference values in healthy young (HY) and elderly (HE) subjects.

    METHODS: Fifty HY subjects (28 females, 21-30 years of age) and 44 HE (23 females, 64-80 years of age) were scanned on a 3-Tesla MR system. The PCMRI sequence had a spatial resolution of 0.35 mm per pixel, with the measurement plan placed perpendicularly to the OA. Mean flow rate (Qmean), resistive index (RI), and arterial volume pulsatility of OA (ΔVmax) were measured from the flow rate curve. Accuracy of PCMRI measures was investigated using a vessel-phantom mimicking the diameter and the flow rate range of the human OA.

    RESULTS: Flow rate could be assessed in 97% of the OAs. Phantom investigations showed good agreement between the reference and PCMRI measurements with an error of <7%. No statistical difference was found in Qmean between HY and HE individuals (HY: mean ± SD = 10.37 ± 4.45 mL/min; HE: 10.81 ± 5.15 mL/min, P = 0.655). The mean of ΔVmax (HY: 18.70 ± 7.24 μL; HE: 26.27 ± 12.59 μL, P < 0.001) and RI (HY: 0.62 ± 0.08; HE: 0.67 ± 0.1, P = 0.012) were significantly different between HY and HE.

    CONCLUSIONS: This study demonstrated that the flow rate of OA can be quantified using PCMRI. There was an age difference in the pulsatility parameters; however, the mean flow rate appeared independent of age. The primary difference in flow curves between HE and HY was in the relaxation phase of the systolic peak.

  • 2.
    Ambarki, Khalid
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Israelsson, Hanna
    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.
    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.
    Brain ventricular size in healthy elderly: comparison between evans index and volume measurement.2010In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 67, no 1, p. 94-99Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A precise definition of ventricular enlargement is important in the diagnosis of hydrocephalus as well as in assessing central atrophy. The Evans index (EI), a linear ratio between the maximal frontal horn width and the cranium diameter, has been extensively used as an indirect marker of ventricular volume (VV). With modern imaging techniques, brain volume can be directly measured. OBJECTIVE: To determine reference values of intracranial volumes in healthy elderly individuals and to correlate volumes with the EI. METHODS: Magnetic resonance imaging (3 T) was performed in 46 healthy white elderly subjects (mean age +/- standard deviation, 71 +/- 6 years) and in 20 patients (74 +/- 7 years) with large ventricles according to visual inspection. VV, relative VV (RVV), and EI were assessed. Ventricular dilation was defined using VV and EI by a value above the 95th percentile range for healthy elderly individuals. RESULTS: In healthy elderly subjects, we found VV = 37 +/- 18 mL, RVV = 2.47 +/- 1.17%, and EI = 0.281 +/- 0.027. Including the patients, there was a strong correlation between EI and VV (R = 0.94) as well as between EI and RVV (R = 0.95). However, because of a wide 95% prediction interval (VV: +/-45 mL; RVV: +/- 2.54%), EI did not give a sufficiently good estimate of VV and RVV. CONCLUSION: VV (or RVV) and the EI reflect different properties. The exclusive use of EI in clinical studies as a marker of enlarged ventricles should be questioned. We suggest that the definition of dilated ventricles in white elderly individuals be defined as VV >77 mL or RVV >4.96 %. Future studies should compare intracranial volumes with clinical characteristics and prognosis.

  • 3.
    Ambarki, Khalid
    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).
    Lindqvist, Tomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. 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 Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Petterson, E
    Warntjes, JBM
    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. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Evaluation of automatic measurement of the intracranial volume based on quantitative MR imaging2012In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 33, no 10, p. 1951-1956Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Brain size is commonly described in relation to ICV, whereby accurate assessment of this quantity is fundamental. Recently, an optimized MR sequence (QRAPMASTER) was developed for simultaneous quantification of T1, T2, and proton density. ICV can be measured automatically within minutes from QRAPMASTER outputs and a dedicated software, SyMRI. Automatic estimations of ICV were evaluated against the manual segmentation.

    MATERIALS AND METHODS: In 19 healthy subjects, manual segmentation of ICV was performed by 2 neuroradiologists (Obs1, Obs2) by using QBrain software and conventional T2-weighted images. The automatic segmentation from the QRAPMASTER output was performed by using SyMRI. Manual corrections of the automatic segmentation were performed (corrected-automatic) by Obs1 and Obs2, who were blinded from each other. Finally, the repeatability of the automatic method was evaluated in 6 additional healthy subjects, each having 6 repeated QRAPMASTER scans. The time required to measure ICV was recorded.

    RESULTS: No significant difference was found between reference and automatic (and corrected-automatic) ICV (P > .25). The mean difference between the reference and automatic measurement was -4.84 ± 19.57 mL (or 0.31 ± 1.35%). Mean differences between the reference and the corrected-automatic measurements were -0.47 ± 17.95 mL (-0.01 ± 1.24%) and -1.26 ± 17.68 mL (-0.06 ± 1.22%) for Obs1 and Obs2, respectively. The repeatability errors of the automatic and the corrected-automatic method were <1%. The automatic method required 1 minute 11 seconds (SD = 12 seconds) of processing. Adding manual corrections required another 1 minute 32 seconds (SD = 38 seconds).

    CONCLUSIONS: Automatic and corrected-automatic quantification of ICV showed good agreement with the reference method. SyMRI software provided a fast and reproducible measure of ICV.

  • 4.
    Ambarki, Khalid
    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).
    Petr, J.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Wirestam, R.
    Zarrinkoob, Laleh
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Malm, Jan
    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).
    Partial Volume Correction of Cerebral Perfusion Estimates Obtained by Arterial Spin Labeling2015In: 16th Nordic-Baltic Conference on Biomedical Engineering: 16. NBC & 10. MTD 2014 joint conferences. October 14-16, 2014, Gothenburg, Sweden, 2015, Vol. 48, p. 17-19Conference paper (Refereed)
    Abstract [en]

    Arterial Spin labeling (ASL) is a fully non-invasive MRI method capable to quantify cerebral perfusion. However, gray (GM) and white matter (WM) ASL perfusions are difficult to assess separately due to limited spatial resolution increasing the partial volume effects (PVE). In the present study, ASL PVE correction was implemented based on a regression algorithm in 22 healthy young men. PVE corrected perfusion of GM and WM were compared to previous studies. PVE-corrected GM perfusion was in agreement with literature values. In general, WM perfusion was higher despite the use of PVE correction.

  • 5.
    Ambarki, Khalid
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wåhlin, Anders
    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.
    MR imaging of brain volumes: evaluation of a fully automatic software2011In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 32, no 2, p. 408-412Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Automatic assessment of brain volumes is needed in researchand clinical practice. Manual tracing is still the criterionstandard but is time-consuming. It is important to validatethe automatic tools to avoid the problems of clinical studiesdrawing conclusions on the basis of brain volumes estimatedwith methodologic errors. The objective of this study was toevaluate a new commercially available fully automatic softwarefor MR imaging of brain volume assessment. Automatic and expertmanual brain volumes were compared.

    MATERIALS AND METHODS: MR imaging (3T, axial T2 and FLAIR) was performed in 41 healthyelderly volunteers (mean age, 70 ± 6 years) and 20 patientswith hydrocephalus (mean age, 73 ± 7 years). The softwareQBrain was used to manually and automatically measure the followingbrain volumes: ICV, BTV, VV, and WMHV. The manual method hasbeen previously validated and was used as the reference. Agreementbetween the manual and automatic methods was evaluated by usinglinear regression and Bland-Altman plots.

    RESULTS: There were significant differences between the automatic andmanual methods regarding all volumes. The mean differences wereICV = 49 ± 93 mL (mean ± 2SD, n = 61), BTV = 11± 70 mL, VV = –6 ± 10 mL, and WMHV = 2.4± 9 mL. The automatic calculations of brain volumes tookapproximately 2 minutes per investigation.

    CONCLUSIONS: The automatic tool is promising and provides rapid assessmentof brain volumes. However, the software needs improvement beforeit is incorporated into research or daily use. Manual segmentationremains the reference method.

  • 6.
    Ambarki, Khalid
    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).
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Zarrinkoob, Laleh
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wirestam, R.
    Petr, J.
    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). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Accuracy of Parenchymal Cerebral Blood Flow Measurements Using Pseudocontinuous Arterial Spin-labeling in Healthy Volunteers2015In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 36, no 10, p. 1816-1821Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The arterial spin-labeling method for CBF assessment is widely available, but its accuracy is not fully established. We investigated the accuracy of a whole-brain arterial spin-labeling technique for assessing the mean parenchymal CBF and the effect of aging in healthy volunteers. Phase-contrast MR imaging was used as the reference method. MATERIALS AND METHODS: Ninety-two healthy volunteers were included: 49 young (age range, 20-30 years) and 43 elderly (age range, 65-80 years). Arterial spin-labeling parenchymal CBF values were averaged over the whole brain to quantify the mean pCBF(ASL) value. Total. CBF was assessed with phase-contrast MR imaging as the sum of flows in the internal carotid and vertebral arteries, and subsequent division by brain volume returned the pCBF(PCMRI) value. Accuracy was considered as good as that of the reference method if the systematic difference was less than 5 mL/min/100 g of brain tissue and if the 95% confidence intervals were equal to or better than +/- 10 mL/min/100 g. RESULTS: pCBF(ASL) correlated to pCBF(PCMRI) (r = 0.73; P < .001). Significant differences were observed between the pCBF(ASL) and pCBF(PCMRI) values in the young (P = .001) and the elderly (P < .001) volunteers. The systematic differences (mean 2 standard deviations) were -4 +/- 14 mL/min/100 g in the young subjects and 6 +/- 12 mL/min/100 g in the elderly subjects. Young subjects showed higher values than the elderly subjects for pCBF(PCMRI) (young, 57 +/- 8 mL/min/100 g; elderly, 54 +/- 7 mL/min/100 g; P = .05) and pCBF(ASL) (young, 61 +/- 10 mL/min/100 g; elderly, 48 +/- 10 mL/min/100 g; P < .001). CONCLUSIONS: The limits of agreement were too wide for the arterial spin-labeling method to be considered satisfactorily accurate, whereas the systematic overestimation in the young subjects and underestimation in the elderly subjects were close to acceptable. The age-related decrease in parenchymal CBF was augmented in arterial spin-labeling compared with phase-contrast MR imaging.

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  • 7.
    Andersson, Kennet
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Manchester, I. R.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Cesarini, K. Giuliana
    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).
    Measurement of CSF dynamics with oscillating pressure infusion2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 128, no 1, p. 17-23Article in journal (Refereed)
    Abstract [en]

    Introduction Infusion tests are used to diagnose and select patients with idiopathic normal pressure hydrocephalus (INPH) for shunt surgery. The test characterizes cerebrospinal fluid dynamics and estimates parameters of the cerebrospinal fluid system, the pressure-volume index (PVI) and the outflow conductance (Cout). The Oscillating Pressure Infusion (OPI) method was developed to improve the test and reduce the investigation time. The aim of this study was to evaluate the new OPI method by comparing it with an established reference method. Methods Forty-seven patients (age 71.2 +/- 8.9years) with communicating hydrocephalus underwent a preoperative lumbar infusion investigation with two consecutive infusion protocols, reference (42min) and new (20min), that is, 94 infusion tests in total. The OPI method estimated Cout and PVI simultaneously. A real-time analysis of reliability was applied to investigate the possibility of infusion time reduction. Results The difference in Cout between the methods was 1.2 +/- 1.8l/s/kPa (Rout=-0.8 +/- 3.5mmHg/ml/min), P<0.05, n=47. With the reliability analysis, the preset 20min of active infusion could have been even further reduced for 19 patients to between 10 and 19min. PVI was estimated to 16.1 +/- 6.9ml, n=47. Conclusions The novel Oscillating Pressure Infusion method produced real-time estimates of Cout including estimates of reliability that was in good agreement with the reference method and allows for a reduced and individualized investigation time.

  • 8.
    Andersson, Kennet
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Manchester, Ian R
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Andersson, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Shiriaev, Anton
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    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.
    Assessment of cerebrospinal fluid outflow conductance using an adaptive observer-experimental and clinical evaluation2007In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 28, no 11, p. 1355-1368Article in journal (Refereed)
    Abstract [en]

    Idiopathic normal pressure hydrocephalus (INPH) patients have a disturbance in the dynamics of the cerebrospinal fluid (CSF) system. The outflow conductance, C, of the CSF system has been suggested to be prognostic for positive outcome after treatment with a CSF shunt. All current methods for estimation of C have drawbacks; these include lack of information on the accuracy and relatively long investigation times. Thus, there is a need for improved methods. To accomplish this, the theoretical framework for a new adaptive observer (OBS) was developed which provides real-time estimation of C. The aim of this study was to evaluate the OBS method and to compare it with the constant pressure infusion (CPI) method. The OBS method was applied to data from infusion investigations performed with the CPI method. These consisted of repeated measurements on an experimental set-up and 30 patients with suspected INPH. There was no significant difference in C between the CPI and the OBS method for the experimental set-up. For the patients there was a significant difference, −0.84 ± 1.25 µl (s kPa)−1, mean ± SD (paired sample t-test, p < 0.05). However, such a difference is within clinically acceptable limits. This encourages further development of this new real-time approach for estimation of the outflow conductance.

  • 9.
    Andersson, Kennet
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Manchester, Ian R
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    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.
    Real-time estimation of cerebrospinal fluid system parameters via oscillating pressure infusion2010In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 48, no 11, p. 1123-1131Article in journal (Refereed)
    Abstract [en]

    Hydrocephalus is related to a disturbed cerebrospinal fluid (CSF) system. For diagnosis, lumbar infusion test are performed to estimate outflow conductance, C (out), and pressure volume index, PVI, of the CSF system. Infusion patterns and analysis methods used in current clinical practice are not optimized. Minimizing the investigation time with sufficient accuracy is of major clinical relevance. The aim of this study was to propose and experimentally evaluate a new method, the oscillating pressure infusion (OPI). The non-linear model of the CSF system was transformed into a linear time invariant system. Using an oscillating pressure pattern and linear system identification methods, C (out) and PVI with confidence intervals, were estimated in real-time. Forty-two OPI and constant pressure infusion (CPI) investigations were performed on an experimental CSF system, designed with PVI = 25.5 ml and variable C (out). The ARX model robustly estimated C (out) (mean C (out,OPI) - C (out,CPI) = 0.08 μl/(s kPa), n = 42, P = 0.68). The Box-Jenkins model proved most reliable for PVI (23.7 ± 2.0 ml, n = 42). The OPI method, with its oscillating pressure pattern and new parameter estimation methods, efficiently estimated C (out) and PVI as well as their confidence intervals in real-time. The results from this experimental study show potential for the OPI method and supports further evaluation in a clinical setting.

  • 10.
    Andersson, Kennet
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Sundström, Nina
    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.
    Effect of resting pressure on the estimate of cerebrospinal fluid outflow conductance2011In: Fluids and barriers of the CNS, ISSN 2045-8118, Vol. 8, no 1, p. 15-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A lumbar infusion test is commonly used as a predictive test for patients with normal pressure hydrocephalus and for evaluation of cerebrospinal fluid (CSF) shunt function. Different infusion protocols can be used to estimate the outflow conductance (Cout) or its reciprocal the outflow resistance, (Rout) with or without using the baseline resting pressure, Pr. Both from a basic physiological research and a clinical perspective, it is important to understand the limitations of the model on which infusion tests are based. By estimating Cout using two different analyses, with or without Pr, the limitations could be explored. The aim of this study was to compare the Cout estimates, and investigate what effect Pr had on the results.

    METHODS: Sixty-three patients that underwent a constant pressure infusion protocol as part of their preoperative evaluation for normal pressure hydrocephalus, were included (age 70.3+/-10.8 years (mean +/-SD). The analysis was performed without (Cexcl Pr) and with (Cincl Pr) Pr. The estimates were compared using Bland-Altman plots and paired sample t-tests (p<0.05 considered significant).

    RESULTS: Mean Cout for the 63 patients was: Cexcl Pr = 7.0+/-4.0 (mean +/-SD) ul/(s kPa) and Cincl Pr = 9.1+/-4.3 ul/(s kPa) and Rout was 19.0+/-9.2 and 17.7+/-11.3 mmHg/ml/min, respectively. There was a positive correlation between methods (r=0.79, n=63, p<0.01). The difference, DeltaCout, -2.1+/-2.7 ul/(s kPa) between methods was significant (p<0.01) and DeltaRout was 1.2 +/- 8.8 mmHg/ml/min). The Bland-Altman plot visualized that the variation around the mean difference was similar all through the range of measured values and there was no correlation between DeltaCout and Cout.

    CONCLUSIONS: The difference between Cout estimates, obtained from analyses with or without Pr, needs to be taken into consideration when comparing results from studies using different infusion test protocols. The study suggests variation in CSF formation rate, variation in venous pressure or a pressure dependent Cout as possible causes for the deviation from the CSF absorption model seen in some patients.

  • 11.
    Andersson, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Grip, Helena
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Lindvall, Peter
    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.
    Brändström, Helge
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Air transport of patients with intracranial air: computer model of pressure effects2003In: Aviation, Space and Environmental Medicine, ISSN 0095-6562, E-ISSN 1943-4448, Vol. 74, no 2, p. 138-144Article in journal (Refereed)
  • 12.
    Andersson, Nina
    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. Neurologi.
    Bäcklund, Tomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Assessment of cerebrospinal fluid outflow conductance using constant-pressure infusion - a method with real time estimation of reliability2005In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 26, no 6, p. 1137-1148Article in journal (Refereed)
  • 13.
    Andersson, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Department of Biomedical Engineering and Informatics, Umeå University Hospital.
    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. Department of Biomedical Engineering and Informatics, Umeå University Hospital.
    Dependency of cerebrospinal fluid outflow resistance on intracranial pressure2008In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 109, no 5, p. 918-922Article in journal (Refereed)
    Abstract [en]

    OBJECT: The outflow resistance (Rout) of the cerebrospinal fluid (CSF) system has generally been accepted by most investigators as independent of intracranial pressure (ICP), but there are also those claiming that it is not. The general belief is that this question has been investigated numerous times in the past, but few studies have actually been specifically aimed at looking at this relationship, and no study has been able to provide scientific evidence to elucidate fully this fundamental and important issue. The objective of this study was to investigate the relationship between ICP and CSF outflow in 30 patients investigated for idiopathic normal-pressure hydrocephalus. METHODS: Lumbar infusion tests with constant pressure levels were performed, and ICP and corresponding flow were measured on 6 pressure levels for each patient. All data were standardized for comparison. RESULTS: In the range of moderate increases from baseline pressure (approximately 5-12 mm Hg, mean baseline pressure 11.7 mm Hg), the assumption of a pressure-independent Rout was confirmed (p = 0.5). However, when the pressure increment from baseline pressure was larger (approximately 15-22 mm Hg), the relationship had a nonlinear tendency (p < 0.05). CONCLUSIONS: The results of this study support the classic textbook theory of a pressure-independent Rout in the normal ICP range, where the CSF system is commonly operating. However, the theory might have to be questioned in regions where ICP exceeds baseline pressure by too much.

  • 14.
    Andersson, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Adaptive method for assessment of cerebrospinal fluid outflow conductance.2007In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 45, no 4, p. 337-343Article in journal (Refereed)
    Abstract [en]

    Outflow conductance (C out) is important for predicting shunt responsiveness in patients with suspected idiopathic adult hydrocephalus syndrome (IAHS). C out is determined by performing an infusion test into the cerebrospinal fluid system, and the reliability of the test is dependent on the measurement time. The objective of this study was to develop an adaptive signal analysis method to reduce the investigation time, by taking the individual intracranial pressure variations of the patient into consideration. The method was evaluated on 28 patients with suspected IAHS. The results from full time investigations (60 min) were compared to the results of the new algorithm. Applying the new adaptive method resulted in a reduction of mean investigation time by 14.3 ± 5.9 min (mean ± SD), p < 0.01. The reduction of reliability in the C out estimation was found clinically negligible. We thus recommend this adaptive method to be used when performing constant pressure infusion tests.

  • 15.
    Arnell, Kai
    et al.
    Department of Paediatric Surgery, University Hospital, Uppsala.
    Koskinen, Lars-Owe D
    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
    Evaluation of Strata NSC and Codman Hakim adjustable cerebrospinal fluid shunts and their corresponding antisiphon devices: laboratory investigation2009In: Journal of Neurosurgery: Pediatrics, ISSN 1933-0707, E-ISSN 1933-0715, Vol. 3, no 3, p. 166-172Article in journal (Refereed)
    Abstract [en]

    OBJECT: The authors investigated and compared the in vitro characteristics of 2 CSF shunts, the Strata NSC and the Codman Hakim, and their corresponding antisiphon devices (ASDs).

    METHODS: Six new CSF shunts and the corresponding ASDs for each model were tested in an automated, computerized experimental setup based on pressure regulation. Opening pressure accuracy, resistance, sensitivity to abdominal pressure, antisiphon effect, and the influence of different ASD positions were determined.

    RESULTS: In general the shunts performed according to the manufacturers' specifications. However, at the lowest setting, the opening pressure of the Strata NSC was close to 0, and in the Codman Hakim shunt, it was higher than specified. The resistance in the Codman Hakim shunt (5.4 mm Hg/ml/min) was much higher than that in the Strata NSC (3.6 mm Hg/ml/min). Abdominal pressure affected opening pressure in both valves. Positioning the Strata ASD above or below the ventricular catheter tip resulted in higher and lower opening pressures, respectively, than when it was placed in line with the catheter. The positioning of the Codman Hakim ASD did not influence the opening pressure.

    CONCLUSIONS: Both CSF shunts work properly, but at the lowest setting the opening pressure of the Strata NSC was near 0 and in the Codman Hakim it was twice the manufacturer's specifications. The resistance in the Strata NSC was below the normal physiological range, and in the Codman Hakim device it was in the lower range of normal. The ASD did not change the shunt characteristics in the lying position and therefore might not do so in children. If this is the case, then a shunt system with an integrated ASD could be implanted at the first shunt insertion, thus avoiding a second operation and the possibility of infection.

  • 16.
    Behrens, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Blekinge Centre of Competence, Blekinge Hospital Karlskrona, Karlskrona, Sweden.
    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.
    Elgh, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Smith, Cynthia
    Williams, Michael A
    Malm, Jan
    A computerized neuropsychological test battery designed for idiopathic normal pressure hydrocephalus2014In: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 11, article id 22Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A tool for standardized and repeated neuropsychological assessments in patients with idiopathic normal pressure hydrocephalus (INPH) is needed. The objective of this study was to develop a computerized neuropsychological test battery designed for INPH and to evaluate its reliability, validity and patient's ability to complete the tests.

    METHODS: Based on a structured review of the literature on neuropsychological testing in INPH, the eight tests most sensitive to the INPH cognitive profile were implemented in a computerized format. The Geriatric Depression Scale (GDS) was also included. Tests were presented on a touch-screen monitor, with animated instructions and speaker sound. The battery was evaluated with the following cohorts: A. Test-retest reliability, 44 healthy elderly; B. Validity against standard pen and pencil testing, 28 patients with various cognitive impairments; C. Ability to complete test battery, defined as completion of at least seven of the eight tests, 40 investigated for INPH.

    RESULTS: A. All except the figure copy test showed good test-retest reliability, r = 0.67-0.90; B. A high correlation was seen between conventional and computerized tests (r = 0.66-0.85) except for delayed recognition and figure copy task; C. Seventy-eight percent completed the computerized battery; Patients diagnosed with INPH (n = 26) performed worse on all tests, including depression score, compared to healthy controls.

    CONCLUSIONS: A new computerized neuropsychological test battery designed for patients with communicating hydrocephalus and INPH was introduced. Its reliability, validity for general cognitive impairment and completion rate for INPH was promising. After exclusion of the figure copy task, the battery is ready for clinical evaluation and as a next step we suggest validation for INPH and a comparison before and after shunt surgery.

    TRIAL REGISTRATION: ClinicalTrials.org NCT01265251.

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  • 17.
    Behrens, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Medicine, Blekinge Hospital, Karlskrona.
    Elgh, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Umeå University, Faculty of Social Sciences, Department of Psychology.
    Leijon, Göran
    Kristensen, Bo
    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).
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    The Computerized General Neuropsychological INPH Test revealed improvement in idiopathic normal pressure hydrocephalus after shunt surgery2020In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 132, no 3, p. 733-740Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE The Computerized General Neuropsychological INPH Test (CoGNIT) provides the clinician and the researcher with standardized and accessible cognitive assessments in patients with idiopathic normal pressure hydrocephalus (INPH). CoGNIT includes tests of memory, executive functions, attention, manual dexterity, and psychomotor speed. Investigations of the validity and reliability of CoGNIT have been published previously. The aim of this study was to evaluate CoGNIT's sensitivity to cognitive change after shunt surgery in patients with INPH.

    METHODS Forty-one patients with INPH (median Mini-Mental State Examination score 26) were given CoGNIT preoperatively and at a postoperative follow-up 4 months after shunt surgery. Scores were compared to those of 44 healthy elderly control volunteers. CoGNIT was administered by either a nurse or an occupational therapist.

    RESULTS Improvement after shunt surgery was seen in all cognitive domains: memory (10-word list test, p < 0.01); executive functions (Stroop incongruent color and word test, p < 0.01); attention (2-choice reaction test, p < 0.01); psychomotor speed (Stroop congruent color and word test, p < 0.01); and manual dexterity (4-finger tapping, p < 0.01). No improvement was seen in the Mini-Mental State Examination score. Preoperative INPH test scores were significantly impaired compared to healthy control subjects (p < 0.001 for all tests).

    CONCLUSIONS In this study the feasibility for CoGNIT to detect a preoperative impairment and postoperative improvement in INPH was demonstrated. CoGNIT has the potential to become a valuable tool in clinical and research work.

  • 18.
    Behrens, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Lenfeldt, Niklas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Ambarki, Khalid
    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.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Transcranial Doppler pulsatility index: not an accurate method to assess intracranial pressure.2010In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 66, no 6, p. 1050-1057Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Transcranial Doppler sonography (TCD) assessment of intracranial blood flow velocity has been suggested to accurately determine intracranial pressure (ICP). OBJECTIVE: We attempted to validate this method in patients with communicating cerebrospinal fluid systems using predetermined pressure levels. METHODS: Ten patients underwent a lumbar infusion test, applying 4 to 5 preset ICP levels. On each level, the pulsatility index (PI) in the middle cerebral artery was determined by measuring the blood flow velocity using TCD. ICP was simultaneously measured with an intraparenchymal sensor. ICP and PI were compared using correlation analysis. For further understanding of the ICP-PI relationship, a mathematical model of the intracranial dynamics was simulated using a computer. RESULTS: The ICP-PI regression equation was based on data from 8 patients. For 2 patients, no audible Doppler signal was obtained. The equation was ICP = 23*PI + 14 (R = 0.22, P < .01, N = 35). The 95% confidence interval for a mean ICP of 20 mm Hg was -3.8 to 43.8 mm Hg. Individually, the regression coefficients varied from 42 to 90 and the offsets from -32 to +3. The mathematical simulations suggest that variations in vessel compliance, autoregulation, and arterial pressure have a serious effect on the ICP-PI relationship. CONCLUSIONS: The in vivo results show that PI is not a reliable predictor of ICP. Mathematical simulations indicate that this is caused by variations in physiological parameters.

  • 19.
    Behrens, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lenfeldt, Niklas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ambarki, Khalid
    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 Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Intracranial Pressure and Pulsatility Index:  2011In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 69, no 4, p. E1033-E1034Article in journal (Refereed)
  • 20.
    Behrens, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lenfeldt, Niklas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskinen, Lars-Owe
    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 Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Are intracranial pressure wave amplitudes measurable through lumbar puncture?2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, no 4, p. 233-241Article in journal (Refereed)
    Abstract [en]

     Objective The aim of this study was to investigate whether pulsations measured in the brain correspond to those measured in lumbar space, and subsequently whether lumbar punctures could replace invasive recordings. Methods In ten patients with normal pressure hydrocephalus, simultaneous recordings of the intracranial pressure (ICP; intraparenchymal) and lumbar pressure (LP; cerebrospinal fluid pressure) were performed. During registration, pressure was altered between resting pressure and 45mmHg using an infusion test. Data were analyzed regarding pulsations (i.e., amplitudes). Also, the pressure sensors were compared in a bench test. Results The correlation between intracranial and lumbar amplitudes was 0.98. At resting pressure, and moderately elevated ICP, intracranial pulse amplitudes exceeded that of lumbar space with about 0.9mmHg. At the highest ICP, the difference changed to 0.2mmHg. The bench test showed that the agreement of sensor readings was good at resting pressure, but reduced at higher amplitudes. Conclusions Compared to intracranial registrations, amplitudes measured through lumbar puncture were slightly attenuated. The bench test showed that differences were not attributable to dissimilarities of the sensor systems. A lumbar pressure amplitude measurement is an alternative to ICP recording, but the thresholds for what should be interpreted as elevated amplitudes need to be adjusted.

  • 21.
    Birnefeld, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Petersson, Karl
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Wåhlin, Anders
    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). Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    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. Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Birnefeld, Elin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Zarrinkoob, Laleh
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Cerebral blood flow assessed with phase-contrast magnetic resonance imaging during blood pressure changes with noradrenaline and labetalol: a trial in healthy volunteers 2023In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175Article in journal (Refereed)
    Abstract [en]

    Background: Adequate cerebral perfusion is central during general anesthesia. However, perfusion is not readily measured bedside. Clinicians currently rely mainly on MAP as a surrogate even though the relationship between blood pressure and cerebral blood flow is not well understood. The aim of this study was to apply phase contrast MRI to characterize blood flow responses in healthy volunteers to commonly used pharmacological agents that increase or decrease arterial blood pressure.

    Methods: Eighteen healthy volunteers aged 30-50 years were investigated with phase contrast MRI. Intraarterial blood pressure monitoring was used. First, intravenous noradrenaline was administered to a target MAP of 20% above baseline. After a wash-out period, intravenous labetalol was given to a target MAP of 15% below baseline. Cerebral blood flow was measured using phase contrast MRI and defined as the sum of flow in the internal carotid arteries and vertebral arteries. CO was defined as the flow in the ascending aorta.

    Baseline median cerebral blood flow was 772 ml/min (interquartile range, 674 to 871), and CO was 5,874 ml/min (5,199 to 6,355). The median dose of noradrenaline was 0.17 µg · kg−1 · h−1 (0.14 to 0.22). During noradrenaline infusion, cerebral blood flow decreased to 705 ml/min (606 to 748; P = 0.001), and CO decreased to 4,995 ml/min (4,705 to 5,635; P = 0.01). A median dose of labetalol was 120 mg (118 to 150). After labetalol boluses, cerebral blood flow was unchanged at 769 ml/min (734 to 900; P = 0.68). CO increased to 6,413 ml/min (6,056 to 7,464; P = 0.03).

    Conclusion: In healthy awake subjects, increasing MAP using intravenous noradrenaline decreased cerebral blood flow and CO. This data does not support inducing hypertension with noradrenaline to increase cerebral blood flow. Cerebral blood flow was unchanged when decreasing MAP using labetalol.

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  • 22.
    Birnefeld, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    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).
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Cerebral arterial pulsatility is associated with features of small vessel disease in patients with acute stroke and TIA: a 4D flow MRI study2020In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 267, no 3, p. 721-730Article in journal (Refereed)
    Abstract [en]

    Cerebral small vessel disease (SVD) is a major cause of stroke and cognitive impairment. However, the underlying mechanisms behind SVD are still poorly understood. High cerebral arterial pulsatility has been suggested as a possible cause of SVD. In population studies, arterial pulsatility has been linked to white matter hyperintensities (WMH), cerebral atrophy, and cognitive impairment, all features of SVD. In stroke, pulsatility data are scarce and contradictory. The aim of this study was to investigate the relationship between arterial pulsatility and SVD in stroke patients. With a cross-sectional design, 89 patients with acute ischemic stroke or TIA were examined with MRI. A neuropsychological assessment was performed 1 year later. Using 4D flow MRI, pulsatile indices (PI) were calculated for the internal carotid artery (ICA) and middle cerebral artery (M1, M3). Flow volume pulsatility (FVP), a measure corresponding to the cyclic expansion of the arterial tree, was calculated for the same locations. These parameters were assessed for associations with WMH volume, brain volume and cognitive function. ICA-FVP was associated with WMH volume (β = 1.67, 95% CI: [0.1, 3.24], p = 0.037). M1-PI and M1-FVP were associated with decreasing cognitive function (β = - 4.4, 95% CI: [- 7.7, - 1.1], p = 0.009 and β = - 13.15, 95% CI: [- 24.26, - 2.04], p = 0.02 respectively). In summary, this supports an association between arterial pulsatility and SVD in stroke patients, and provides a potential target for further research and preventative treatment. FVP may become a useful biomarker for assessing pulsatile stress with PCMRI and 4D flow MRI.

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  • 23.
    Björnfot, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
    Larsson, Jenny
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Hansson, William
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Birnefeld, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    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. Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
    Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults: a 4D flow MRI study2024In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016Article in journal (Refereed)
    Abstract [en]

    White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66–85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV’s stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.

  • 24.
    Björnfot, Cecilia
    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.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Assessing cerebral arterial pulse wave velocity using 4D flow MRI2021In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 41, no 10, p. 2769-2777Article in journal (Refereed)
    Abstract [en]

    Intracranial arterial stiffening is a potential early marker of emerging cerebrovascular dysfunction and could be mechanistically involved in disease processes detrimental to brain function via several pathways. A prominent consequence of arterial wall stiffening is the increased velocity at which the systolic pressure pulse wave propagates through the vasculature. Previous non-invasive measurements of the pulse wave propagation have been performed on the aorta or extracranial arteries with results linking increased pulse wave velocity to brain pathology. However, there is a lack of intracranial “target-organ” measurements. Here we present a 4D flow MRI method to estimate pulse wave velocity in the intracranial vascular tree. The method utilizes the full detectable branching structure of the cerebral vascular tree in an optimization framework that exploits small temporal shifts that exists between waveforms sampled at varying depths in the vasculature. The method is shown to be stable in an internal consistency test, and of sufficient sensitivity to robustly detect age-related increases in intracranial pulse wave velocity.

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  • 25.
    Dunås, Tora
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Holmgren, Madelene
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    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).
    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).
    Accuracy of blood flow assessment in cerebral arteries with 4D flow MRI: Evaluation with three segmentation methods2019In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 50, no 2, p. 511-518Article in journal (Refereed)
    Abstract [en]

    Background: Accelerated 4D flow MRI allows for high‐resolution velocity measurements with whole‐brain coverage. Such scans are increasingly used to calculate flow rates of individual arteries in the vascular tree, but detailed information about the accuracy and precision in relation to different postprocessing options is lacking.

    Purpose: To evaluate and optimize three proposed segmentation methods and determine the accuracy of in vivo 4D flow MRI blood flow rate assessments in major cerebral arteries, with high‐resolution 2D PCMRI as a reference.

    Study Type: Prospective.

    Subjects: Thirty‐five subjects (20 women, 79 ± 5 years, range 70–91 years).

    Field Strength/Sequence: 4D flow MRI with PC‐VIPR and 2D PCMRI acquired with a 3 T scanner.

    Assessment: We compared blood flow rates measured with 4D flow MRI, to the reference, in nine main cerebral arteries. Lumen segmentation in the 4D flow MRI was performed with k‐means clustering using four different input datasets, and with two types of thresholding methods. The threshold was defined as a percentage of the maximum intensity value in the complex difference image. Local and global thresholding approaches were used, with evaluated thresholds from 6–26%.

    Statistical Tests: Paired t‐test, F‐test, linear correlation (P < 0.05 was considered significant) along with intraclass correlation (ICC).

    Results: With the thresholding methods, the lowest average flow difference was obtained for 20% local (0.02 ± 15.0 ml/min, ICC = 0.97, n = 310) or 10% global (0.08 ± 17.3 ml/min, ICC = 0.97, n = 310) thresholding with a significant lower standard deviation for local (F‐test, P = 0.01). For all clustering methods, we found a large systematic underestimation of flow compared with 2D PCMRI (16.1–22.3 ml/min).

    Data Conclusion: A locally adapted threshold value gives a more stable result compared with a globally fixed threshold. 4D flow with the proposed segmentation method has the potential to become a useful reliable clinical tool for assessment of blood flow in the major cerebral arteries.

    Level of Evidence: 2

    Technical Efficacy: Stage 2

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  • 26.
    Dunås, Tora
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Zarrinkoob, Laleh
    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 Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Automatic labeling of cerebral arteries in magnetic resonance angiography2016In: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 29, no 1, p. 39-47Article in journal (Refereed)
    Abstract [en]

    In order to introduce 4D flow magnetic resonance imaging (MRI) as a standard clinical instrument for studying the cerebrovascular system, new and faster postprocessing tools are necessary. The objective of this study was to construct and evaluate a method for automatic identification of individual cerebral arteries in a 4D flow MRI angiogram. Forty-six elderly individuals were investigated with 4D flow MRI. Fourteen main cerebral arteries were manually labeled and used to create a probabilistic atlas. An automatic atlas-based artery identification method (AAIM) was developed based on vascular-branch extraction and the atlas was used for identification. The method was evaluated by comparing automatic with manual identification in 4D flow MRI angiograms from 67 additional elderly individuals. Overall accuracy was 93 %, and internal carotid artery and middle cerebral artery labeling was 100 % accurate. Smaller and more distal arteries had lower accuracy; for posterior communicating arteries and vertebral arteries, accuracy was 70 and 89 %, respectively. The AAIM enabled fast and fully automatic labeling of the main cerebral arteries. AAIM functionality provides the basis for creating an automatic and powerful method to analyze arterial cerebral blood flow in clinical routine.

  • 27.
    Dunås, Tora
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    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).
    Zarrinkoob, Laleh
    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 Medicine, Department of Radiation Sciences. 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).
    A Stereotactic Probabilistic Atlas for the Major Cerebral Arteries2017In: Neuroinformatics, ISSN 1539-2791, E-ISSN 1559-0089, Vol. 15, no 1, p. 101-110Article in journal (Refereed)
    Abstract [en]

    Improved whole brain angiographic and velocity-sensitive MRI is pushing the boundaries of noninvasively obtained cerebral vascular flow information. The complexity of the information contained in such datasets calls for automated algorithms and pipelines, thus reducing the need of manual analyses by trained radiologists. The objective of this work was to lay the foundation for such automated pipelining by constructing and evaluating a probabilistic atlas describing the shape and location of the major cerebral arteries. Specifically, we investigated how the implementation of a non-linear normalization into Montreal Neurological Institute (MNI) space improved the alignment of individual arterial branches. In a population-based cohort of 167 subjects, age 64-68 years, we performed 4D flow MRI with whole brain volumetric coverage, yielding both angiographic and anatomical data. For each subject, sixteen cerebral arteries were manually labeled to construct the atlas. Angiographic data were normalized to MNI space using both rigid-body and non-linear transformations obtained from anatomical images. The alignment of arterial branches was significantly improved by the non-linear normalization (p < 0.001). Validation of the atlas was based on its applicability in automatic arterial labeling. A leave-one-out validation scheme revealed a labeling accuracy of 96 %. Arterial labeling was also performed in a separate clinical sample (n = 10) with an accuracy of 92.5 %. In conclusion, using non-linear spatial normalization we constructed an artery-specific probabilistic atlas, useful for cerebral arterial labeling.

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  • 28.
    Dunås, Tora
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    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).
    Zarrinkoob, Laleh
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ambarki, Khalid
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). 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, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Towards Automatic Identification of Cerebral Arteries in 4D Flow MRI2015In: 16th Nordic-Baltic Conference on Biomedical Engineering / [ed] Henrik Mindedal, Mikael Persson, 2015, Vol. 48, p. 40-43Conference paper (Refereed)
    Abstract [en]

    4D flow MRI is a powerful imaging technique which provides an angiographic image with information about blood flow in a large volume, time resolved over the cardiac cycle, in a short imaging time. This study aims to develop an automatic method for identification of cerebral arteries. The proposed method is based on an atlas of twelve arteries, developed from 4D flow MRI of 25 subjects. The atlas was constructed by normalizing all images to MNI-space, manually identifying the arteries and creating an average over the volume. The identification is done by extracting a vascular skeleton from the image, transforming it to MNI-space, labeling it with the atlas and transforming it back to subject space. The method was evaluated on a pilot cohort of 8 subjects. The rate of correctly identified arteries was 97%.

  • 29.
    Dunås, Tora
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå Universitet.
    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).
    Zarrinkoob, Laleh
    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 Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    4D flow MRI: automatic assessment of blood flow in cerebral arteries2019In: Biomedical Engineering & Physics Express, E-ISSN 2057-1976, Vol. 5, no 1, article id 015003Article in journal (Refereed)
    Abstract [en]

    Objective: With a 10-minute 4D flow MRI scan, the distribution of blood flow to individual arteries throughout the brain can be analyzed. This technique has potential to become a biomarker for treatment decisions, and to predict prognosis after stroke. To efficiently analyze and model the large dataset in clinical practice, automatization is needed. We hypothesized that identification of selected arterial regions using an atlas with a priori probability information on their spatial distribution can provide standardized measurements of blood flow in the main cerebral arteries.

    Approach: A new method for automatic placement of measurement locations in 4D flow MRI was developed based on an existing atlas-based method for arterial labeling, by defining specific regions of interest within the corresponding arterial atlas. The suggested method was evaluated on 38 subjects with carotid artery stenosis, by comparing measurements of blood flow rate at automatically selected locations to reference measurements at manually selected locations.

    Main results: Automatic and reference measurement ranged from 10 to 580 ml min−1 and were highly correlated (r = 0.99) with a mean flow difference of 0.61 ± 10.7 ml min−1 (p = 0.21). Out of the 559 arterial segments in the manual reference, 489 were correctly labeled, yielding a sensitivity of 88%, a specificity of 85%, and a labeling accuracy of 87%.

    Significance: This study confirms that atlas-based labeling of 4D flow MRI data is suitable for efficient flow quantification in the major cerebral arteries. The suggested method improves the feasibility of analyzing cerebral 4D flow data, and fills a gap necessary for implementation in clinical use.

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  • 30. Edsbagge, Mikael
    et al.
    Andreasson, Ulf
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wikkelsø, Carsten
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Blennow, Kaj
    Zetterberg, Henrik
    Tullberg, Mats
    Alzheimer's Disease-Associated Cerebrospinal Fluid (CSF) Biomarkers do not Correlate with CSF Volumes or CSF Production Rate2017In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 58, no 3, p. 821-828Article in journal (Refereed)
    Abstract [en]

    Background: Neuropathologically, Alzheimer's disease (AD) is characterized by accumulation of a 42 amino acid peptide called amyloid-beta (A beta(42)) in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuronal degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the volumes and production rates of which vary considerably between individuals, by reduced concentration of A beta(42), increased concentration of phosphorylated tau (P-tau) protein, and increased concentration of total tau (T-tau) protein, respectively. Objective: To examine the outstanding question if CSF concentrations of AD associated biomarkers are influenced by variations in CSF volumes, CSF production rate, and intracranial pressure in healthy individuals. Methods: CSF concentrations of A beta(42), P-tau, and T-tau, as well as a number of other AD-related CSF biomarkers were analyzed together with intracranial subarachnoid, ventricular, and spinal CSF volumes, as assessed by magnetic resonance imaging volumetric measurements, and CSF production rate in 19 cognitively normal healthy subjects (mean age 70.6, SD 3.6 years). Results: Negative correlations were seen between the concentrations of three CSF biomarkers (albumin ratio, A beta(38), and A beta(40)), and ventricular CSF volume, but apart from this finding, no significant correlations were observed. Conclusion: These results speak against inter-individual variations in CSF volume and production rate as important confounds in the AD biomarker research field.

  • 31. Eklund, A
    et al.
    Ågren Wilsson, A
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Andersson, N
    Bergenheim, AT
    Koskinen, LO
    Malm, J
    Two computerized methods used to analyze intracranial pressure B waves: comparison with traditional visual interpretation2001In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 94, no 3, p. 392-396Article in journal (Refereed)
    Abstract [en]

    OBJECT: Slow and rhythmic oscillations in intracranial pressure (ICP), also known as B waves, have been claimed to be one of the best preoperative predictive factors in idiopathic adult hydrocephalus syndrome (IAHS). Definitions of B waves vary widely, and previously reported results must be treated with caution. The aims of the present study were to develop a definition of B waves, to develop a method to estimate the B-wave content in an ICP recording by using computer algorithms, and to validate these procedures by comparison with the traditional visual interpretation. METHODS: In eight patients with IAHS, ICP was continuously monitored for approximately 20 hours. The ICP B-wave activity as a percentage of total monitoring time (B%) was estimated by using visual estimation according to the definition given by Lundberg, and also by using two computer algorithms (Methods I and II). In Method I each individual wave was classified as a B wave or not, whereas Method II was used to estimate the B-wave content by evaluating the B-wave power in 10-minute blocks of ICP recordings. CONCLUSIONS: The two computerized algorithms produced similar results. However, with the amplitude set to 1 mm Hg, Method I yielded the highest correlation with the visual analysis (r = 0.74). At least 5 hours of monitoring time was needed for an acceptable approximation of the B% in an overnight ICP recording. The advantages of using modern technology in the analysis of B-wave content of ICP are obvious and these methods should be used in future studies.

  • 32.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Resonator sensor technique for medical use: an intraocular pressure measurement system2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the work of this doctoral dissertation a new resonator sensor technique, first presented in 1989, has been further developed and evaluated with focus on technical characteristics and applications within the medical field.

    In a first part a catheter-type tactile sensor using the resonator sensor technique was evaluated in a silicone model and applied to human prostate in vitro. The main finding was that different histological compositions of prostate tissue correlated with the frequency shift, .fS, of the resonator sensor and that the common property was the hardness of the tissue. The results indicated that hardness of the prostate tissue, and maybe hardness of human tissue in general, can be expressed according to a cone penetration standard (DIN ISO 2137) and that the hardness can be measured with this tactile sensor system. The tissue hardness application for the resonator sensor technique has to be further developed and evaluated in a larger study. The study also produced results that has led to the basic understanding of the resonator sensor system. One important result was that .fS of the sensor system was related to the contact area between sensor and sample. This indicated that the resonance sensor could be used for contact area measurement.

    In a second part, containing three studies, the area-sensing capability from the first study was utilised in the development and evaluation of the applanation resonator sensor (ARS) for measurement of intraocular pressure (IOP). For the purpose of evaluating IOP-tonometers, an in vitro pig-eye model was developed, and it was shown that a saline column connected to the vitreous chamber could be used successfully to induce variations in IOP.

    A ARS sensor with a flat contact surface was applied onto the cornea with constant force and .fS was measured. A mathematical model based on the Imbert-Fick law and the assumption that .fS was linearly related to contact area was proposed and verified with a convincing result. IOP measured with the ARS correlated well (r=0.92, n=360) with the IOP elicited by a saline column.

    The ARS in a constant-force arrangement was evaluated on healthy human subjects in vivo. The results verified the sensor principle but revealed a nonnegligible source of error in off-centre positioning between the sensor and cornea. The sensor probe was redesigned and evaluated in the in vitro model. The new probe, with a spherical contact surface against the eye reduced the sensitivity to off-centre positioning. It was also shown that a .fS normalisation procedure could reduce the between-eye differences.

    The ARS method for IOP measurement was further developed using combined continuous force and area measurement during the dynamic phase when the sensor initially contacts the cornea. A force sensor was included with the resonator sensor in one probe. Evaluation was performed with the in vitro pig-eye model. The hypothesis was that the IOP could be deduced from the differential change of force and area during that phase. The study showed good accuracy and good reproducibility with a correlation of r=0.994 (n=414) between measured pressure in the vitreous chamber and IOP according to the ARS. Measurement time was short, 77 ms after initial contact. Problems with inter-eye differences and low resolution at high pressures were reduced. The ARS method is the first to combine simultaneous, continuous sampling of both parameters included in the applanation principle. Consequently, there is a potential for reducing errors in the clinical IOP tonometry.

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  • 33.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bergh, A
    Lindahl, O A
    A catheter tactile sensor for measuring hardness of soft tissue: measurement in a silicone model and in an in vitro human prostate model.1999In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 37, no 5, p. 618-24Article in journal (Refereed)
    Abstract [en]

    Tissue hardness is related to tissue composition, and this is often changed by disease. It is therefore of interest to measure the hardness in an objective and non-invasive way. A tactile sensor based on a vibrating piezoelectric ceramic element in a feedback loop is described. When the sensor touches an object it produces a frequency shift related to the hardness of the object. The aim of this study was to develop an in vitro hardness measurement method using a catheter type version of the sensor. The method was evaluated in an established silicone tissue model and on human prostate tissue in vitro. A linear relationship was found with a high degree of explanation (R2 = 0.98) between a cone penetration hardness standard (DIN ISO 2137) applied to the silicone model and the corresponding frequency shift. The results from measurements on a human prostate tissue sample, fixed with formalin, showed that the relative hardness measured with the tactile sensor correlated (R = -0.96, p < 0.001, N = 60) with the proposed hardness related to the histological composition of the prostate tissue. The results indicated that hardness of prostate tissue, and maybe hardness of human tissue in general, can be expressed according to the cone penetration standard and that the hardness can be measured with this tactile sensory system. These findings hold the promise of further development of a non-invasive tool for hardness measurement in a clinical situation.

  • 34.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bäcklund, T
    Lindahl, O A
    A resonator sensor for measurement of intraocular pressure--evaluation in an in vitro pig-eye model.2000In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 21, no 3, p. 355-67Article in journal (Refereed)
    Abstract [en]

    Intraocular pressure (IOP) measurement is performed routinely at every eye clinic. High IOP, which can be a sign of glaucoma, can lead to degeneration of the retina and can cause blindness. In this study we developed a resonator sensor for IOP measurement based on an oscillator consisting of a piezoelectric element made of lead zirconate titanate, a flat contact piece of nylon and a feedback circuit. The aim of this study was to evaluate the new sensor's ability to determine lOP in an in vitro pig-eye model. Six eyes from four pigs were removed and fixed in agar. They were then pressurized by a saline column (10-35 cm H2O) through a cannula inserted into the vitreous chamber. The IOP was measured with the resonator sensor applied to cornea. An Alcon applanation pneumatonometer and a standard Viggo-Spectramed pressure sensor connected to the saline column were used as references. The IOP as measured with the resonator sensor correlated well with the pressure elicited by the saline column for individual eyes (r = 0.96-0.99, n = 60) and for all eyes (r = 0.92, n = 360). The correlation between the resonance sensor and the pneumatonometer was r = 0.92 (n = 360). The pneumatonometer also showed a good correlation with the saline column (r = 0.98, n = 360). We conclude that our in vitro pig-eye model made it possible to induce reproducible variation in IOP, and measurement of that pressure with the newly developed resonator sensor gave very promising results for development of a clinically applicable IOP tonometer with unique properties.

  • 35.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Bäcklund, Tomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Heart centrum, Umeå universitet.
    Natural angioplasty as a mechanical effect of exercise2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, no 3, p. 3083-3085Article in journal (Refereed)
  • 36.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindahl, Olof A.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    An applanation resonator sensor for measuring intraocular pressure using combined continuous force and area measurement2003In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, no 7, p. 3017-3024Article in journal (Refereed)
  • 37.
    Eklund, Anders
    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).
    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, Pharmacology.
    Holmlund, Petter
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    The Pressure Difference between Eye and Brain Changes with Posture2016In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 80, no 2, p. 269-276Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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  • 38.
    Eklund, Anders
    et al.
    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, Neurosurgery.
    Williams, Michael A
    Luciano, Mark G
    Dombrowski, Stephen M
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hydrodynamics of the CertasTM programmable valve for the treatment of hydrocephalus2012In: Fluids and barriers of the CNS, ISSN 2045-8118, Vol. 9, no 1, p. 12-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The new CertasTM shunt for the treatment of hydrocephalus has seven standard pressure settings that according to the manufacturer range from 36 to 238 mmH2O, and an additional "Virtual Off" setting with an opening pressure >400 mmH2O. Information on actual pressure response and reliability of shunt performance is important in clinical application, especially the "Virtual Off" setting as a non-surgical replacement for shunt ligation. The objective of this study was to evaluate the in-vitro hydrodynamic performance of the CertasTM shunt.

    METHODS: Six new CertasTM shunts with proximal and distal catheters were tested with an automated, computerized test system that raised the pressure from zero to a maximum pressure and back to zero at each valve setting. Opening pressure and flow resistance were determined.

    RESULTS: For settings 1-7 the measured opening pressure range was 26 to 247 mmH2O, and the mean change in opening pressure for a one-step adjustment was between 33 and 38 mmH2O. For setting 8 ("Virtual Off") the measured mean opening pressure was 494 +/- 34 mmH2O (range 451 to 556 mmH2O). The mean outflow resistance was 7.0 mmHg/ml/min (outflow conductance 17.9 ul/s/kPa).

    CONCLUSIONS: The six shunts had similar characteristics and closely matched the manufacturer's specifications for opening pressure at settings 1-7. The opening pressure for the "Virtual Off" setting was nearly 500 mmH2O, which is 100 mmH2O higher than the manufacturer's specification of ">400" and should be functionally off for most patients with communicating hydrocephalus. Clinical studies are needed to evaluate if the CSF dynamic profile persists after implantation in patients.

  • 39.
    Eklund, Anders
    et al.
    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.
    Malm, J
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Features of the Sinushunt and its influence on the cerebrospinal fluid system2004In: J Neurol Neurosurg Psychiatry, ISSN 0022-3050, Vol. 75, no 8, p. 1156-1159Article in journal (Refereed)
    Abstract
  • 40.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Bäcklund, Tomas
    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).
    Lindahl, Olof A
    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).
    Evaluation of applanation resonator sensors for intra-ocular pressure measurement: results from clinical and in vitro studies.2003In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 41, no 2, p. 190-197Article in journal (Refereed)
    Abstract [en]

    Glaucoma is an eye disease that, in its most common form, is characterised by high intra-ocular pressure (IOP), reduced visual field and optic nerve damage. For diagnostic purposes and for follow-up after treatment, it is important to have simple and reliable methods for measuring IOP. Recently, an applanation resonator sensor (ARS) for measuring IOP was introduced and evaluated using an in vitro pig-eye model. In the present study, the first clinical evaluation of the same probe has been carried out, with experiments in vivo on human eyes. There was a low but significant correlation between IOP(ARS) and the IOP measured with a Goldmann applanation tonometer (r = 0.40, p = 0.001, n = 72). However, off-centre positioning of the sensor against the cornea caused a non-negligible source of error. The sensor probe was redesigned to have a spherical, instead of flat, contact surface against the eye and was evaluated in the in vitro model. The new probe showed reduced sensitivity to off-centre positioning, with a decrease in relative deviation from 89% to 11% (1 mm radius). For normalised data, linear regression between IOP(ARS) and direct IOP measurement in the vitreous chamber showed a correlation of r = 0.97 (p < 0.001, n = 108) and a standard deviation for the residuals of SD < or = 2.18 mm Hg (n = 108). It was concluded that a spherical contact surface should be preferred and that further development towards a clinical instrument should focus on probe design and signal analysis.

  • 41.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lundkvist, B.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Malm, J
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Infusion technique can be used to distinguish between dysfunction of a hydrocephalus shunt system and a progressive dementia2004In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 42, no 5, p. 644-649Article in journal (Refereed)
    Abstract [en]

    In a deteriorating shunted patient with hydrocephalus, an investigation of shunt function is often performed to distinguish a dysfunctioning shunt from an aggravated condition of the disease. The paper illustrates how a lumbar cerebrospinal fluid (CSF) infusion method can be used to evaluate post-operative deterioration in a shunted patient in order to give the physician valuable support in the shunt revision decision. A 77-year-old man with hydrocephalus was treated operatively by the insertion of a CSF shunt. Owing to shunt failure, the shunt was revised twice during a 5 year period. Using a computerised infusion technique method, with two needles placed in the lumbar subarachnoid space, the CSF dynamic system was determined pre- and post-operatively with the functioning as well as the dysfunctioning shunts. The data were verified with a bench-test of the extirpated CSF shunt. There was a significant difference in conductance G between CSF systems with an open shunt and CSF systems with no shunt or an occluded shunt (ΔG=38mm3 s−1 kPa−1, p=0.014, n=7, ANOVA). CSF dynamics investigations, with and without a shunt, can give valuable clinical support in the management of a deteriorating hydrocephalus patient. With further development of the lumbar infusion method moving towards easy-to-use equipment, there is potential for widespread clinical use.

  • 42.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences.
    Smielewski, Peter
    Chambers, Iain
    Alperin, Noam
    Malm, Jan
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurology.
    Czosnyka, Marek
    Marmarou, Anthony
    Assessment of cerebrospinal fluid outflow resistance.2007In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 45, no 8, p. 719-735Article in journal (Refereed)
  • 43.
    Ekman, Urban
    et al.
    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 Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Fordell, Helena
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lenfeldt, Niklas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wåhlin, Anders
    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).
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Increase of frontal neuronal activity in chronic neglect after training in virtual reality2018In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 4, p. 284-292Article in journal (Refereed)
    Abstract [en]

    Objectives: A third of patients with stroke acquire spatial neglect associated with poor rehabilitation outcome. New effective rehabilitation interventions are needed. Scanning training combined with multisensory stimulation to enhance the rehabilitation effect is suggested. In accordance, we have designed a virtual-reality based scanning training that combines visual, audio and sensori-motor stimulation called RehAtt((R)). Effects were shown in behavioural tests and activity of daily living. Here, we use fMRI to evaluate the change in brain activity during Posners Cuing Task (attention task) after RehAtt((R)) intervention, in patients with chronic neglect.

    Methods: Twelve patients (mean age=72.7years, SD=6.1) with chronic neglect (persistent symptoms >6months) performed the interventions 3 times/wk during 5weeks, in total 15hours. Training effects on brain activity were evaluated using fMRI task-evoked responses during the Posners cuing task before and after the intervention.

    Results: Patients improved their performance in the Posner fMRI task. In addition, patients increased their task-evoked brain activity after the VR interventions in an extended network including pre-frontal and temporal cortex during attentional cueing, but showed no training effects during target presentations.

    Conclusions: The current pilot study demonstrates that a novel multisensory VR intervention has the potential to benefit patients with chronic neglect in respect of behaviour and brain changes. Specifically, the fMRI results show that strategic processes (top-down control during attentional cuing) were enhanced by the intervention. The findings increase knowledge of the plasticity processes underlying positive rehabilitation effects from RehAtt((R)) in chronic neglect.

  • 44.
    el Azazi, Mildred
    et al.
    S:t Erik, Stockholm.
    Wang, Ling
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wachtmeister, Lillemor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Background light adaptation of the retinal neuronal adaptive system. II. Dynamic effects2004In: Documenta Ophthalmologica, ISSN 0012-4486, Vol. 109, no 2, p. 201-213Article in journal (Refereed)
    Abstract [en]

    The dynamic effects of continuous exposure to light on the neuronal adaptive system of the retina, as indicated by the oscillatory response (OPs) of the electroretinogram (ERG) were studied in the albino rat. Digitally filtered OPs and the a- and b-waves of the corneal ERG were simultaneously recorded in dark adaptation, during continuous light adaptation to four levels of background light (BGL) changing in steps of two log units from 1.43 x 10(-6) cd/m2, referred to as 'low and high scotopic, low and high mesopic' levels. Exposed to 'high scotopic' BGL the total oscillatory response (SOP) significantly enhanced within the first minute, whereas the amplitudes of the a- and b-waves were unaffected. In 'low mesopic' BGL the SOP increased within the first minute, whereas the a- and b-waves significantly decreased. 'High mesopic' BGL instantaneously and profoundly reduced both the SOP and the slow potentials. The individual OPs changed in amplitudes mainly within the first minute of BGL. In general, the earlier OPs (O1 and O2) reacted more to the two 'scotopic' BGL levels, whereas the later OPs (O3 and 04) were more affected by the relatively brighter two 'mesopic' conditions. In conclusion, the rapid increase of the OPs within the first minute of 'high scotopic' and 'low mesopic' BGL exposure may represent a rudimentary light adaptational effect in the rod-dominated rat retina. These findings also suggest that the neuronal adaptive mechanism of the retina seems to be a robust system, probably attaining preservation of visual abilities in the rat on exposure to light.

  • 45.
    Farahmand, Dan
    et al.
    Hydrocephalus Research Unit, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Qvarlander, Sara
    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.
    Wikkelsö, Carsten
    Hydrocephalus Research Unit, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Tisell, Magnus
    Hydrocephalus Research Unit, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Intracranial pressure in hydrocephalus: impact of shunt adjustments and body positions2015In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 86, no 2, p. 222-228Article in journal (Refereed)
    Abstract [en]

    Background The association between intracranial pressure (ICP) and different shunt valve opening pressures in relation to body positions is fundamental for understanding the physiological function of the shunt.

    Objective To analyse the ICP and ICP wave amplitude (AMP) at different shunt settings and body positions in patients with hydrocephalus.

    Methods In this prospective study 15 patients with communicating hydrocephalus were implanted with a ligated adjustable ventriculoperitoneal shunt. They also received a portable intraparenchymatous ICP-monitoring device. Postoperative ICP and AMP were recorded with the patients in three different body positions (supine, sitting and walking) and with the shunt ligated and open at high, medium and low valve settings. In each patient 12 10 min segments were coded, blinded and analysed for mean ICP and mean AMP using an automated computer algorithm.

    Results Mean ICP and mean AMP were lower at all three valve settings compared with the ligated shunt state (p<0.001). Overall, when compared with the supine position, mean ICP was 11.5 +/- 1.1 (mean +/- SD) mm Hg lower when sitting and 10.5 +/- 1.1 mm Hg lower when walking (p<0.001). Mean ICP was overall 1.1 mm Hg higher (p=0.042) when walking compared with sitting. The maximal adjustability difference (highest vs lowest valve setting) was 4.4 mm Hg.

    Conclusions Changing from a supine to an upright position reduced ICP while AMP only increased at trend level. Lowering of the shunt valve opening pressure decreased ICP and AMP but the difference in mean ICP in vivo between the highest and lowest opening pressures was less than half that previously observed in vitro.

  • 46.
    Fordell, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bodin, Kenneth
    Umeå University, Faculty of Science and Technology, Department of Computing Science. Umeå University, Faculty of Science and Technology, High Performance Computing Center North (HPC2N).
    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.
    RehAtt – scanning training for neglect enhanced by multi-sensory stimulation in Virtual Reality2016In: Topics in Stroke Rehabilitation, ISSN 1074-9357, E-ISSN 1945-5119, Vol. 23, no 3, p. 191-199Article in journal (Refereed)
    Abstract [en]

    Background: There is a lack of effective treatment for neglect. We have developed a new training method, RehAtt (TM). The objective of this study was to determine whether RehAtt (TM) improves spatial attention in chronic neglect after stroke. Methods: RehAtt (TM) consists of a computer with monitor, 3D glasses, and a force feedback interface (Robotic pen) giving sensory motor activation to the contra-lesional arm. The software combines visual scanning training with multi-sensory stimulation in 3D virtual reality (VR) game environment. Fifteen stroke patients with chronic neglect (duration > 6 month) had repeated baseline evaluations to confirm stability of symptoms. There were no test-retest effects for any of the tests. Thereafter, all patients trained 15 h in RehAtt (TM) (3 x 1 h for 5 weeks). A neglect test battery and Catherine Bergego Scale, CBS, were used to assess behavioral outcome after intervention. CBS was also used at a 6-month follow-up. Results: Using repeated measurement analysis improvements due to the training were found for Star cancellation test (p = 0.006), Baking tray task (p < 0.001), and Extinction test (p = 0.05). In the Posner task improvements were seen fewer missed targets (p = 0.024). CBS showed improvements in activities of daily life immediately after training (p < 0.01). After 6 months the patients still reported improvement in CBS. Conclusion: RehAtt (TM) is a new concept for rehabilitation of neglect. Training with the VR-method improved spatial attention and showed transfer to improved spatial attention in activities of daily living in chronic neglect. Our results are promising and merit further studies.

  • 47.
    Gasslander, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Departments of Cardiology and Health, Medicine and Caring Services, Linkoping University, Vrinnevi General Hospital Norrköping.
    Sundström, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Risk factors for developing subdural hematoma: a registry-based study in 1457 patients with shunted idiopathic normal pressure hydrocephalus2021In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 134, no 2, p. 668-677Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Subdural hematomas and hygromas (SDHs) are common complications in idiopathic normal pressure hydrocephalus (iNPH) patients with shunts. In this registry-based study, patients with shunted iNPH were screened nationwide to identify perioperative variables that may increase the risk of SDH.

    METHODS: The Swedish Hydrocephalus Quality Registry was reviewed for iNPH patients who had undergone shunt surgery in Sweden in 2004-2014. Potential risk factors for SDH were recorded preoperatively and 3 months after surgery. Drug prescriptions were identified from a national pharmacy database. Patients who developed SDHs were compared with those without SDHs.

    RESULTS: The study population consisted of 1457 patients, 152 (10.4%) of whom developed an SDH. Men developed an SDH more often than women (OR 2.084, 95% CI 1.421-3.058, p < 0.001). Patients on platelet aggregation inhibitors developed an SDH more often than those who were not (OR 1.733, 95% CI 1.236-2.431, p = 0.001). At surgery, shunt opening pressures had been set 5.9 mm H2O lower in the SDH group than in the no-SDH group (109.6 ± 24.1 vs 115.5 ± 25.4 mm H2O, respectively, p = 0.009). Antisiphoning devices (ASDs) were used in 892 patients but did not prevent SDH. Mean opening pressures at surgery and the follow-up were lower with shunts with an ASD, without causing more SDHs. No other differences were seen between the groups.

    CONCLUSIONS: iNPH patients in this study were diagnosed and operated on in routine practice; thus, the results represent everyday care. Male sex, antiplatelet medication, and a lower opening pressure at surgery were risk factors for SDH. Physical status and comorbidity were not. ASD did not prevent SDH, but a shunt with an ASD allowed a lower opening pressure without causing more SDHs.

  • 48. Gehlen, Manuel
    et al.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Kurtcuoglu, Vartan
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Schmid Daners, Marianne
    Comparison of anti-siphon devices: how do they affect CSF dynamics in supine and upright posture?2017In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 159, no 8, p. 1389-1397Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Three different types of anti-siphon devices (ASDs) have been developed to counteract siphoning-induced overdrainage in upright posture. However, it is not known how the different ASDs affect CSF dynamics under the complex pressure environment seen in clinic due to postural changes. We investigated which ASDs can avoid overdrainage in upright posture best without leading to CSF accumulation.

    METHODS: Three shunts each of the types Codman Hakim with SiphonGuard (flow-regulated), Miethke miniNAV with proSA (gravitational), and Medtronic Delta (membrane controlled) were tested. The shunts were compared on a novel in vitro setup that actively emulates the physiology of a shunted patient. This testing method allows determining the CSF drainage rates, resulting CSF volume, and intracranial pressure in the supine, sitting, and standing posture.

    RESULTS: The flow-regulated ASDs avoided increased drainage by closing their primary flow path when drainage exceeded 1.39 ± 0.42 mL/min. However, with intraperitoneal pressure increased in standing posture, we observed reopening of the ASD in 3 out of 18 experiment repetitions. The adjustable gravitational ASDs allow independent opening pressures in horizontal and vertical orientation, but they did not provide constant drainage in upright posture (0.37 ± 0.03 mL/min and 0.26 ± 0.03 mL/min in sitting and standing posture, respectively). Consequently, adaptation to the individual patient is critical. The membrane-controlled ASDs stopped drainage in upright posture. This eliminates the risk of overdrainage, but leads to CSF accumulation up to the volume observed without shunting when the patient is upright.

    CONCLUSIONS: While all tested ASDs reduced overdrainage, their actual performance will depend on a patient's specific needs because of the large variation in the way the ASDs influence CSF dynamics: while the flow-regulated shunts provide continuous drainage in upright posture, the gravitational ASDs allow and require additional adaptation, and the membrane-controlled ASDs show robust siphon prevention by a total stop of drainage.

  • 49. Hallberg, Per
    et al.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Bäcklund, Tomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Clinical evaluation of applanation resonance tonometry: a comparison with Goldmann applanation tonometry.2007In: Journal of glaucoma, ISSN 1057-0829, E-ISSN 1536-481X, Vol. 16, no 1, p. 88-93Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purpose of this study was to calibrate and evaluate the precision of the new applanation resonance tonometry (ART) in a clinical study designed in accordance with the International Standard Organization's requirements. METHODS: This was a prospective, randomized, single-center study, where healthy volunteers and patients participated. A total of 153 eyes were divided into 3 groups with respect to their intraocular pressure (IOP) at screening: <16 mm Hg, 16 to 23 mm Hg, and >23 mm Hg. IOP was measured with Goldmann applanation tonometry (GAT) as reference method and by ART in both a biomicroscope (ARTBiom) and a handheld (ARTHand) setup with a 10-minutes pause between methods. The mean of 6 readings was regarded as one measurement value. RESULTS: Mean age of the subjects was 59 years (range 20 to 87 y). GAT showed a mean IOP of 20.0 mm Hg (range 8.5 to 43.5 mm Hg, n=153). The precision was 2.07 mm Hg for ARTBiom and 2.50 mm Hg for ARTHand, with a significant dependency for age as compared with GAT. Measurement order produced a decreasing IOP with a mean of 2.3 mm Hg between the first and last method. CONCLUSIONS: The precision obtained in both ARTBiom and ARTHand was within the limits set by the International Standard Organization standards for tonometers. The standardized procedure and the stability of the biomicroscope setup resulted in a slightly better precision as compared with the handheld setup. Despite a 10-minutes pause between measurements, the order was a significant factor, possibly because the patients were more apprehensive at the first measurement.

  • 50.
    Hallberg, Per
    et al.
    Department of Biomedical Engineering and Informatics, University Hospital, Umeå, Sweden.
    Eklund, Anders
    Department of Biomedical Engineering and Informatics, University Hospital, Umeå, Sweden.
    Santala, Kenneth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Koskela, Timo
    Lindahl, Olof A.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Underestimation of intraocular pressure after photorefractive keratectomy: a biomechanical analysis2006In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 44, p. 609-618Article in journal (Refereed)
    Abstract [en]

    Excimer laser surgery, to correct corneal refraction, induces changes in corneal thickness and curvature. Both factors can cause measurement errors when determining intraocular pressure (IOP). This study evaluates effects of photorefractive keratectomy (PRK) on IOP measurements, using Goldmann applanation tonometry (GAT) and Applanation resonance tonometry (ART), in an in vitro model. Six porcine eyes was enucleated and pressurised to a constant IOP = 30 mmHg. After removal of the epithelium, the eyes were PRK-treated for a total of 25 dioptres. The measured IOP decreased 13.2 mmHg for GAT and 9.0 mmHg for ART. The total underestimation by GAT was larger than for ART, and a part of the ART underestimation (3.5 mmHg) was assigned to sensitivity to the change in corneal surface structure resulting from the removal of epithelium. The flat contact probe of GAT, as compared with the convex tip of ART, provided explanation for the difference in IOP measurement error after PRK.

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