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  • 1.
    Ambarki, Khalid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hallberg, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Lindén, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Zarrinkoob, Laleh
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Blood flow of ophthalmic artery in healthy individuals determined by phase-contrast magnetic resonance imaging2013Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 54, nr 4, s. 2738-2745Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Israelsson, Hanna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Brain ventricular size in healthy elderly: comparison between evans index and volume measurement.2010Ingår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 67, nr 1, s. 94-99Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Lindqvist, Tomas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Petterson, E
    Warntjes, JBM
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Evaluation of automatic measurement of the intracranial volume based on quantitative MR imaging2012Ingår i: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 33, nr 10, s. 1951-1956Artikel i tidskrift (Refereegranskat)
    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 universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    MR imaging of brain volumes: evaluation of a fully automatic software2011Ingår i: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 32, nr 2, s. 408-412Artikel i tidskrift (Refereegranskat)
    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.

  • 5.
    Brynolfsson, Patrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nilsson, David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Hauksson, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Karlsson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Garpebring, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Nyholm, Tufve
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Asklund, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    ADC texture-An imaging biomarker for high-grade glioma?2014Ingår i: Medical physics (Lancaster), ISSN 0094-2405, Vol. 41, nr 10, s. 101903-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose:

    Survival for high-grade gliomas is poor, at least partly explained by intratumoral heterogeneity contributing to treatment resistance. Radiological evaluation of treatment response is in most cases limited to assessment of tumor size months after the initiation of therapy. Diffusion-weighted magnetic resonance imaging (MRI) and its estimate of the apparent diffusion coefficient (ADC) has been widely investigated, as it reflects tumor cellularity and proliferation. The aim of this study was to investigate texture analysis of ADC images in conjunction with multivariate image analysis as a means for identification of pretreatment imaging biomarkers.

    Methods:

    Twenty-three consecutive high-grade glioma patients were treated with radiotherapy (2 Gy/60 Gy) with concomitant and adjuvant temozolomide. ADC maps and T1-weighted anatomical images with and without contrast enhancement were collected prior to treatment, and (residual) tumor contrast enhancement was delineated. A gray-level co-occurrence matrix analysis was performed on the ADC maps in a cuboid encapsulating the tumor in coronal, sagittal, and transversal planes, giving a total of 60 textural descriptors for each tumor. In addition, similar examinations and analyses were performed at day 1, week 2, and week 6 into treatment. Principal component analysis (PCA) was applied to reduce dimensionality of the data, and the five largest components (scores) were used in subsequent analyses. MRI assessment three months after completion of radiochemotherapy was used for classifying tumor progression or regression.

    Results:

    The score scatter plots revealed that the first, third, and fifth components of the pretreatment examinations exhibited a pattern that strongly correlated to survival. Two groups could be identified: one with a median survival after diagnosis of 1099 days and one with 345 days, p = 0.0001.

    Conclusions:

    By combining PCA and texture analysis, ADC texture characteristics were identified, which seems to hold pretreatment prognostic information, independent of known prognostic factors such as age, stage, and surgical procedure. These findings encourage further studies with a larger patient cohort. (C) 2014 Author(s).

  • 6.
    de Flon, Pierre
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Gunnarsson, Martin
    Laurell, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Söderström, Lars
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Lindqvist, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Krauss, Wolfgang
    Dring, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bergman, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab2016Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 87, nr 2, s. 141-147Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To describe the effects of switching treatment from ongoing first-line injectable therapies to rituximab on inflammatory activity measured by MRI and levels of CSF neurofilament light chain (CSF-NFL) in a cohort of patients with clinically stable relapsing-remitting multiple sclerosis (RRMS).

    Method: Seventy-five patients with clinically stable RRMS treated with the first-line injectables interferon-β (IFN-β) and glatiramer acetate (GA) at 3 Swedish centers were switched to rituximab in this open-label phase II multicenter study. After a run-in period of 3 months, 2 IV doses of 1,000 mg rituximab were given 2 weeks apart followed by repeated clinical assessment, MRI, and CSF-NFL for 24 months.

    Results: The mean cumulated number of gadolinium-enhancing lesions per patient at months 3 and 6 after treatment shift to rituximab was reduced compared to the run-in period (0.028 vs 0.36, p = 0.029). During the first year after treatment shift, the mean number of new or enlarged T2 lesions per patient was reduced (0.01 vs 0.28, p = 0.004) and mean CSF-NFL levels were reduced by 21% (p = 0.01).

    Conclusions: For patients with RRMS, a treatment switch from IFN or GA to rituximab is associated with reduced inflammatory activity measured by MRI and CSF-NFL.

    Classification of evidence: This study provides Class IV evidence that rituximab has an equal or superior effect in reducing inflammatory activity in RRMS measured by MRI and CSF-NFL compared to first-line injectables during the first year after treatment shift.

  • 7.
    Dunås, Tora
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Zarrinkoob, Laleh
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Automatic labeling of cerebral arteries in magnetic resonance angiography2016Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 29, nr 1, s. 39-47Artikel i tidskrift (Refereegranskat)
    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.

  • 8.
    Israelsson, Hanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Ventriculomegaly and balance disturbances in patients with TIA2012Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 125, nr 3, s. 163-170Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives -  Dilated ventricles and gait disturbances are common in the elderly, and these are also features of the treatable syndrome idiopathic normal pressure hydrocephalus (INPH). Many studies report an association between hypertension, vascular disease and INPH. The objective of this study was to study the frequency of ventriculomegaly, with or without hydrocephalic symptoms, in patients who had suffered from a transitory ischaemic attack (TIA).

    Methods -  Gait, Romberg sign, tandem standing and one-leg stance were consecutively evaluated in elderly >24 h after a TIA. Ventricular size, white matter lesions and atrophy were assessed on computed tomography scans. Exclusion criteria were conditions possibly influencing the balance tests.

    Results -  Seventy-six patients with TIA out of 105 were included. Ventriculomegaly [Evans Index (EI) > 0.30] was observed in 19.7% and very large ventricles (EI > 0.33) in 7.9%. Ventriculomegaly was found in 58% of the patients with a previous 'history of balance or gait disturbance', but only in 12% of those without any prior disturbance (chi-square test; P = 0.0009). Three out of 76 patients with TIA (3.9%) fulfilled both radiological and clinical criteria for 'possible INPH'.

    Conclusion -  Ventriculomegaly is a common finding in elderly. One out of 20 patients with TIA may suffer from INPH, existing before and independent of the TIA diagnosis. Therefore, patients presenting with ventriculomegaly and gait/balance disturbances not attributable to other causes should be referred to a hydrocephalus centre or a neurologist with special interest in INPH.

  • 9.
    Jakobson Mo, Susanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Edenbandt, Lars
    Göteborgs Universitet, Avdelningen för molekylär och klinisk medicin.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    123I-FP-Cit and 123I-IBZM SPECT uptake in a prospective normal material analysed with two different semi-quantitative image evaluation tools2013Ingår i: Nuclear medicine communications, ISSN 0143-3636, E-ISSN 1473-5628, Vol. 34, nr 10, s. 978-989Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The need for age-adjusted and/or sex-adjusted reference values in dopamine transporter (DAT) and dopamine D2 receptor (D2R) imaging with single-photon emission computed tomography (SPECT) in a longitudinal study of parkinsonian diseases was investigated. We used two different image evaluation tools with a cross-sectional and longitudinal statistical approach.

    Materials and methods: Baseline DAT and/or D2R SPECT were performed in 51 healthy controls (HC), age-matched to patients in an ongoing prospective study on idiopathic parkinsonism. Twenty-four HC were re-examined after 3 years and 21 HC were examined again after 5 years. SPECT was performed with I-123-FP-Cit and I-123-IBZM on a two-headed hybrid gamma camera. Regions of interest and volumes of interest (VOIs) were used for image evaluation. A cross-sectional and longitudinal statistical analysis was carried out.

    Results: Fewer sex-based differences and less age dependency were seen in DAT SPECT uptake ratios compared with D2R SPECT uptake ratios and when comparing uptake ratios obtained with regions of interest against those with VOIs. In the cross-sectional analysis, a significant age-dependent decline was seen in women in both DAT and D2R uptakes with the VOI method but not in men with either evaluation method. In the longitudinal dataset, both a slight decline and increase over time were seen in DAT uptake; however, a general pattern of decrease was seen in both men and women in D2R uptake.

    Conclusion: The choice of the image evaluation method can influence the pattern of sex-based and age-related differences. The results speak for the use of age-stratified reference values for women, in particular when using a VOI method.

  • 10.
    Johansson, Elias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Bahrami, Nazila
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Cerebral microbleeds in idiopathic normal pressure hydrocephalus2016Ingår i: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 13, artikel-id UNSP 4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: A vascular disease could be involved in pathophysiology of normal pressure hydrocephalus (INPH). If so, there should be an association between INPH and cerebral microbleeds (CMB). This study aims to analyze if CMB are associated with INPH.

    Methods: In this case-control study we included 14 patients with INPH (mean age 76 years, 60 % female) and 41 healthy controls (HeCo; mean age 71 years, 60 % female). All were investigated with magnetic resonance imaging (MRI) using a T2*-sequence. The MRI exams were reviewed by two neuroradiologists for the presence of CMBs; the prevalence of findings of two or more CMBs was compared between INPH group and control group. After investigation, INPH patients underwent shunt surgery.

    Results: Two or more CMB were detected more frequently in the INPH group compared to HeCo (n = 6, 43 % vs. n = 4, 10 %; p = 0.01). Among the participants where MRI revealed CMB, the number of CMB was higher among the INPH patients than the HeCo (median 8; IQR 2-34 vs. median 1; IQR 1-2; p = 0.005).

    Conclusions: This study supports a vascular component to the pathophysiology of INPH.

  • 11.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hansson, William
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Three-day CSF drainage barely reduces ventricular size in normal pressure hydrocephalus2012Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 79, nr 3, s. 237-242Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

  • 12.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hansson, William
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Diffusion tensor imaging and correlations to Parkinson rating scales2013Ingår i: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 260, nr 11, s. 2823-2830Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The contribution of various brain areas to the overall progression of Parkinson's disease remains to be determined. In this study, we apply MRI diffusion tensor imaging to investigate how alterations in diffusion relate to phenotype and symptoms measured by clinical rating scales. Sixty-four patients were investigated at baseline and three follow-ups (1, 3 and 5 years). Thirty-six patients remained in the last follow-up. Regions of interests included frontal white matter, basal ganglia, thalamus, and cerebellum. Scoring on the Unified Parkinson's Disease Rating Scale (UPDRS) I, II, III, Hoehn and Yahr (HY) scale and the Schwab and England scale (SE) was determined. Mean, radial, and axial diffusion and fractional anisotropy were modeled with phenotype and clinical scales in a multivariate/univariate analysis correcting for other covariates. Significance was set at 0.05 Bonferroni corrected. All rating scales except UPDRS III significantly correlated to the diffusion measures, as did clinical phenotype. Specifically, putamen, globus pallidus, and thalamus demonstrated higher diffusion with worsening scores. Diffusion in thalamus was higher in the tremor dominant phenotype than in postural imbalance and gait disturbance. Decline in overall functionality (UPDRS II and SE scale), including mental status (UPDRS I) and stage of the disease (HY scale), in Parkinson's disease is related to altered diffusion in the lentiform nucleus and thalamus. Motor function is not mirrored in diffusion changes, possibly due to medication. Tremor dominant PD patients show diffusion alterations in the thalamus, but the significance of this for tremor generation remains to be determined.

  • 13.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Neurologi.
    Hauksson, Jón
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Eklund, Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Neurologi.
    Improvement after cerebrospinal fluid drainage is related to levels of N-acetyl-aspartate in idiopathic normal pressure hydrocephalus2008Ingår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 62, nr 1, s. 135-142Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

  • 14.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Holmlund, Henny
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Frontal white matter injuries predestine gait difficulties in Parkinson's disease2016Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 134, nr 3, s. 210-218Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: This study applies diffusion tensor imaging (DTI) to determine differences in neuronal integrity between motor phenotypes in Parkinson's disease. Material and Methods: One hundred and twenty-two patients (47 females, mean age = 70.3 years) were included at baseline. Forty patients were tremor dominant (TD), 64 had postural imbalance and gait difficulty (PIGD), and 18 patients were indeterminate. The DTI was repeated after one, three and 5 years, including reassessment of phenotype. DTI was quantified using fractional anisotropy (FA), and mean, radial and axial diffusion. Targeted white matter involved six regions of interests (ROIs) in prefrontal cortex (PFC), the entrance to the external capsule (EEC) and lateral to the horn of the anterior ventricle (LVAH). Grey matter involved the basal ganglia. Data were analysed using mixed linear models with P < 0.05 (Bonferroni corrected) as significance threshold. Results: PIGD and Indeterminate had reduced FA and axial diffusion in PFC, EEC and LVAH compared to Tremor dominant (P < 0.05). Basal ganglia showed no differences. Post hoc analysis showed that FA correlated negatively, and mean and radial diffusion positively, to PIGD symptoms in EEC, LVAH and four ROIs in PFC (P < 0.05). Tremor symptoms showed no correlations. Patients converting to PIGD and Indeterminate had lower FA, and higher mean and radial diffusion, at baseline in EEC, LVAH and four areas in PFC compared to non-converting patients (P < 0.05). Conclusion: Degeneration in frontal white matter is connected to PIGD symptoms in Parkinson's disease and if present at an early stage, the risk for conversion to the PIGD phenotype increases.

  • 15.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Idiopathic normal pressure hydrocephalus: increased supplementary motor activity accounts for improvement after CSF drainage.2008Ingår i: Brain, ISSN 1460-2156, Vol. 131, nr Pt 11, s. 2904-2912Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 16.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Eklund, Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Diffusion tensor imaging reveals supplementary lesions to frontal white matter in Idiopathic normal pressure hydrocephalus2011Ingår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 68, nr 6, s. 1586-1593Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 17.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Diffusion measures in early stage parkinsonism: controversial findings including hemispheric lateralisation2013Ingår i: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 19, nr 4, s. 469-471Artikel i tidskrift (Refereegranskat)
  • 18.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Fractional anisotropy in the substantia nigra in Parkinson's disease: a complex picture2015Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 22, nr 10, s. 1410-1416Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose: This study employs magnetic resonance imaging (MRI) diffusion tensor imaging to compare diffusion measures in the brains of patients with Parkinson's disease (PD) with healthy controls using longitudinal data. Methods: One-hundred and twenty-two patients and 34 controls were included at baseline. The MRI investigations were repeated after 1, 3 and 5 years. The diffusion measures were quantified using fractional anisotropy and mean, radial and axial diffusion (FA, MD, RD, AD). Regions of interest included the anterior, middle and posterior substantia nigra (SN), but also other areas. Linear models were used to test for the effect of disease and hemispheric lateralization. The P value was set at 0.05 (Bonferroni corrected). Results: Fractional anisotropy and AD were increased in the three nigral subareas in PD (P < 0.01), but MD and RD were unaltered. The right SN had higher FA than the left in all subareas (P < 0.01). MD and AD were increased in the right anterior part (P < 0.04), whereas MD and RD were decreased in the right middle and posterior parts (P < 0.001). The left middle cerebellar peduncle had increased FA and AD (P < 0.001) and decreased MD and RD (P < 0.01) compared to the right. Diffusion measures did not progress over time and side differences were not related to disease or lateralization of symptoms. Conclusions: Increased FA in the SN in PD indicates gliosis and inflammation in the nuclei, but possibly also intrusion of surrounding fibres into the shrinking structure. The hemispheric side differences of diffusion might reflect natural lateralization of connectivity, but their relation to PD must be studied further.

  • 19.
    Linder, Jan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Olsson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Larsson, Ann-Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Edström, Mona
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Degenerative changes were common in brain magnetic resonance imaging in patients with newly diagnosed Parkinson's disease in a population-based cohort2009Ingår i: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 256, nr 10, s. 1671-1680Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to investigate newly diagnosed patients with Parkinson's disease (PD) with structural magnetic resonance imaging (MRI), to compare them with healthy controls, to relate the findings to clinical subtypes - tremor dominant (TD) or postural instability and gait difficulty (PIGD) - and to investigate the relationship between both the duration from onset of symptoms to diagnosis and the severity of symptoms and the MRI findings. Patients with a definite PD diagnosis were compared to patients with a probable PD diagnosis. We hypothesized that the PIGD subtype, the probable PD group, a greater symptom severity and a longer symptom duration would all be associated with more frequent pathological findings. Sixty-six PD patients were included and examined with MRI, 35 with the PIGD subtype and 23 with the TD subtype. Fifty-three had definite PD and 13 probable PD. Thirty healthy individuals, matched for age and sex, served as controls. Degenerative changes in the cerebellar cortex and the superior cerebellar peduncle were significantly more common in the probable PD group than in the controls, suggesting the possibility of an emerging atypical parkinsonian disorder. No significant MRI differences were found between definite PD and controls, between definite PD and probable PD, nor between PIGD and TD. No significant associations were found between duration to diagnosis and MRI results, nor between severity of symptoms and MRI results. Thus, although pathological MRI findings were common they can not be used to separate subgroups of PD in newly diagnosed patients.

  • 20.
    Lindvall, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Borota, Ljubisa
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Jonasson, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Ridderheim, Per-Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Long-Term Follow-Up of Intracranial Aneurysms Treated With Endovascular Coiling: Experience From One Institution2012Ingår i: Vascular and endovascular surgery, ISSN 1538-5744, Vol. 46, nr 4, s. 325-328Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Our aim was to evaluate the long-term treatment results in patients with intracranial aneurysms treated with endovascular techniques. Methods: Forty-four patients treated due to intracranial aneurysms between 1996 and 2002 were investigated with a time-of-flight sequence magnetic resonance angiography (TOF MRA). Results: Depending on the assessment, 47% to 51% of the treated aneurysms had a residual neck at the last digital subtraction angiography follow-up. There was filling of the aneurysm base (2%) in only 1 patient, whereas the remaining aneurysms were totally occluded. A TOF MRA performed 6 to 14 (mean 9.68) years after the last procedure showed a stable result in 93.9% of the treated aneurysms. There were no de novo aneurysms and previously untreated aneurysms were unchanged in size. Conclusion: Our long-term follow-up showed a stable result in previously coiled intracranial aneurysms.

  • 21.
    Lindvall, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Runnerstam, Magnus
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    The Fisher grading correlated to outcome in patients with subarachnoid haemorrhage2009Ingår i: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 23, nr 2, s. 188-192Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cerebral vasospasm is the major cause of delayed ischemia in patients with subarachnoid haemorrhage (SAH). The Fisher grading scale has been used to predict patients in risk of developing vasospasm. Improved radiological techniques and treatment may have changed the relevance of the Fisher scale. We have now evaluated the Fisher scale, Hunt and Hess and age in relation to outcome in patients with SAH. Eighty- three patients were admitted with SAH during two years, and 84 aneurysms were treated in 78 patients. The Glasgow outcome score (GOS) within 3 months were as follows; GOS 1 (19%), GOS 2 (2%), GOS 3 (11%), GOS 4 (9%), GOS 5 (59%). There was a significant correlation between both the Fisher grading scale, Hunt and Hess scale and outcome. Age was not correlated to the Fisher grading scale or the Hunt and Hess scale. Age was also not correlated to outcome in our patients. Despite the correlation to outcome both Hunt and Hess and the Fisher grading scale had a limited predictive value of outcome due to a low specificity and/or sensitivity.

  • 22.
    Lundkvist, Bo
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Cerebrospinal fluid dynamics and long-term survival of the Strata(®) valve in idiopathic normal pressure hydrocephalus.2011Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 124, nr 2, s. 115-121Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 23.
    Malm, Jan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Jacobsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Reference values for CSF outflow resistance and intracranial pressure in healthy elderly2011Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 76, nr 10, s. 903-909Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 24.
    Nyberg, Lars
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Eriksson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Sundström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Riklund Åhlström, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Comparing 1,5T and 3T BOLD fMRI imaging of finger tapping with familiar and novel sequences.2007Ingår i: Neuroscience Imaging, ISSN 1556-4010, Vol. 2, nr 1, s. 53-64Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It has been suggested that fMRI at 3T yields stronger and more extensive BOLD activations than fMRI at 1.5T, and that imaging at higher field strengths can reveal unique activations. In the present study we compared, within-subjects, activation patterns during a finger-tapping task at 1.5 and 3T. The data were analyzed with a random-effects model in SPM2. At a strict statistical level (p<0.05, FWE correction for multiple comparisons), ipsilateral cerebellar activation was revealed at 1.5T. At 3T, activation in sensory-motor regions in the contra-lateral cerebrum was identified in addition to the activation in cerebellum. At a less stringent statistical threshold, imaging at 1.5T and 3T revealed overlapping cortical regions with more extensive clusters at 3T. A similar pattern was seen in a comparison of familiar and novel sequences. However, subcortical activations of thalamus and parts of the basal ganglia were uniquely identified at 3T. Analyses at the individual level substantiated the group results by showing that the higher sensitivity of the 3T resulted in images with higher between-individual consistency in activation patterns.

  • 25.
    Qvarlander, Sara
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Jacobsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Cerebrospinal fluid and blood flow patterns in idiopathic normal pressure hydrocephalus2017Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 135, nr 5, s. 576-584Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

  • 26.
    Qvarlander, Sara
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jacobsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Differences in cerebral blood flow and CSF flow between INPH and healthy elderlyManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

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

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

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

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

  • 27.
    Sandvik, Ulrika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Rosendal, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Logopedi.
    van Doorn, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Logopedi.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Thalamotomy for essential tremor: a very long-term follow-upManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background: DBS (deep brain stimulation) is currently the golden standard in the surgical treatment of ET (essential tremor). Despite the benefits of DBS, there remain situations where lesional surgery may provide an alternative.

    Objective: To perform a very long-term retrospective evaluation of thalamotomies for ET.

    Methods: Nine patients who underwent thalamotomy for ET during 1972–1999 (follow-up period 20.8 ± 5.2 years) were assessed with regard to tremor scores, side effects, and quality of life, as well as lesion size and location.

    Results: All patients had tremor recurrence, although hand function remained slightly better on the treated side than on the non-treated side. Side effects that could be attributed to the procedure were frequent and did in some cases result in a disability for the patient. Quality of life was poorer in this group than in an age-adjusted healthy population. No correlation between lesion size, location, and long-term outcome could be established.

    Conclusions: In this study population the benefits of thalamotomies were limited, while complications were frequent.

  • 28.
    Sandvik, Ulrika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Rosendal, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Logopedi.
    van Doorn, Janis
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Logopedi.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Thalamotomy for essential tremor: a very long-term follow-up2012Ingår i: The Open Neurosurgery Journal, ISSN 1876-5297, Vol. 5, s. 1-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lesional procedures in the thalamus (thalamotomies)were introduced in 1954 by Hassler in the treatment of Parkinsoniantremor and were later also used for ET [1]. After theintroduction of Deep Brain Stimulation (DBS) by Benabid in1987, this technique has gradually replaced lesional surgeryand DBS is at present the treatment of choice for ET [2].DBS is considered to be a reversible technique with fewerrisks, especially in bilateral procedures [3]. Disadvantages ofDBS includehardware related complications, the high cost ofthe procedure, and the more cumbersome life-long follow-up[4]. The American Academy of Neurology gives thalamotomyevidence class C (probably effective) in a recent guidelineupdate [5].For these reasons lesional surgery has recentlybeen discussed as an alternative to DBS in certainselected cases [4].We have therefore decided to review thelong-term results of thalamotomies performed at our departmentby scoring the present symptoms and describing thepresence of persistent neurological deficits which might beattributed to the procedure.

  • 29.
    Sundström, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Venous and cerebrospinal fluid flow in multiple sclerosis. A case-control study.2010Ingår i: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 68, nr 2, s. 255-259Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 30.
    Svenningsson, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bergman, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Dring, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vågberg, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Lindqvist, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bergenheim, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Rapid depletion of B lymphocytes by ultra-low-dose rituximab delivered intrathecally2015Ingår i: Neurology: Neuroimmunology and neuroinflammation, ISSN 0948-6259, E-ISSN 2332-7812, Vol. 2, nr 2, artikel-id e79Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: We are conducting an open-label phase 1b study on the efficacy of intrathecal (IT) administration of rituximab, provided via an Ommaya reservoir, for the treatment of progressive multiple sclerosis (PMS). The objective of this initial study was to monitor B lymphocytes in peripheral blood (PB) and CSF from the first 10 patients 1 year posttreatment.

    Methods: Dose titration was performed with daily escalation from 1 mg to 25 mg IT rituximab (n=3). Lymphocyte subpopulations were monitored daily during dose escalation in PB by flow cytometry and subsequently every 3 months for 1 year, after a total dose of 3 x 25 mg. PB B-lymphocyte subpopulations for the remaining patients (n = 7) were monitored at regular intervals. CSF lymphocyte subpopulations for all patients were monitored by flow cytometry every 2-3 months.

    Results: The PB B-lymphocyte count dropped rapidly after the first 2 injections (total dose of 3.5 mg IT rituximab) to undetectable levels. Three 25-mg doses given once per week depleted peripheral B lymphocytes entirely for the following 3-6 month period.

    Conclusions: Monoclonal antibodies seem to rapidly redistribute to the peripheral compartment following IT injection. Ultra-low doses of rituximab given IT are sufficient to cause complete depletion of peripheral B lymphocytes, indicating that low-dose IT treatment has the potential to be effective in both the CNS and systemic compartments.

    Classification of evidence: This study provides Class IV evidence that for patients with PMS, rituximab provided via an Ommaya reservoir depletes peripheral blood B lymphocytes.

  • 31.
    Vågberg, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Lindqvist, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Brain parenchymal fraction in an age-stratified healthy population: determined by MRI using manual segmentation and three automated segmentation methods2016Ingår i: Journal of neuroradiology, ISSN 0150-9861, E-ISSN 1773-0406, Vol. 43, nr 6, s. 384-391Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND PURPOSE: Brain atrophy is a prominent feature in many neurodegenerative diseases, such as multiple sclerosis, but age-related decrease of brain volume occurs regardless of pathological neurodegeneration. Changes in brain volume can be described by use of the brain parenchymal fraction (BPF), most often defined as the ratio of total brain parenchyma to total intracranial space. The BPF is of interest both in research and in clinical practice. To be able to properly interpret this variable, the normal range of BPF must be known. The objective of this study is to present normal values for BPF, stratified by age, and compare manual BPF measurement to three automated methods. MATERIALS AND METHODS: The BPFs of 106 healthy individuals aged 21 to 85 years were determined by the automated segmentation methods SyMap, VBM8 and SPM12. In a subgroup of 54 randomly selected individuals, the BPF was also determined by manual segmentation. RESULTS: The median (IQR) BPFs of the whole study population were 0.857 (0.064), 0.819 (0.028) and 0.784 (0.073) determined by SyMap, VBM8 and SPM12, respectively. The BPF decreased with increasing age. The correlation coefficients between manual segmentation and SyMap, VBM8 and SPM12 were 0.93 (P<0.001), 0.77 (P<0.001) and 0.56 (P<0.001), respectively. CONCLUSIONS: There was a clear relationship between increasing age and decreasing BPF. Knowledge of the range of normal BPF in relation to age group will help in the interpretation of BPF data. The automated segmentation methods displayed varying degrees of similarity to the manual reference, with SyMap being the most similar.

  • 32.
    Vågberg, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Axelsson, M.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Burman, J.
    Cananau, C.
    Forslin, Y.
    Granberg, T.
    Gunnarsson, M.
    von Heijne, A.
    Jönsson, L.
    Karrenbauer, V. D.
    Larsson, E. -M
    Lindqvist, T.
    Lycke, J.
    Lönn, L.
    Mentesidou, E.
    Müller, S.
    Nilsson, P.
    Piehl, F.
    Svenningsson, A.
    Vrethem, M.
    Wikström, J.
    Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society2017Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 135, nr 1, s. 17-24Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care.

  • 33.
    Vågberg, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Granåsen, Gabriel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Svenningsson, Rasmus
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Lindqvist, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Prediction of disability increase in a real world multiple sclerosis cohortManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    BACKGROUND Multiple sclerosis (MS) is an autoimmune disease characterized by demyelinating CNS-lesions and neurodegeneration. Brain atrophy measurements have been demonstrated to provide prognostic information. Assessment of brain atrophy via magnetic resonance imaging (MRI) using the Brain Parenchymal Fraction (BPF) was added to the clinical follow-up of individuals with MS at Umeå University Hospital in 2009/2010.  

    OBJECTIVE To investigate whether an increase in disability, measured by a short to medium term increase in EDSS, can be predicted using clinically available variables.  To assess if the previously described association between brain atrophy and disability could be detected in the setting of the clinical care program at Umeå University Hospital.

    METHODS All adult MS patients with simultaneous data on BPF, lesion count and EDSS at least at one occasion (n=278) were included. Individuals with two (n=163) and three (n=68) time points with complete data were used for testing the ability to predict Expanded Disability Status Scale (EDSS) score longitudinally.

     RESULTS The EDSS was found to correlate with BPF (p<0.001). Progressive disease course and early EDSS-worsening (SPMS), but no other clinical variables, could predict subsequent EDSS-worsening over follow-up times of approximately 1 to 4 years.

    CONCLUSION BPF was associated with concurrent EDSS, as previously described. Progressive disease course predicted risk for EDSS-increase but it was otherwise very difficult to predict increased disability in this treated MS-cohort. We discuss possible reasons for the lack of predictive value from clinically used variables in a treated MS cohort. 

  • 34.
    Vågberg, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lindqvist, T.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Warntjes, J. B. M.
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Automated Determination of Brain Parenchymal Fraction in Multiple Sclerosis2013Ingår i: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 34, nr 3, s. 498-504Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND PURPOSE: Brain atrophy is a manifestation of tissue damage in MS. Reduction in brain parenchymal fraction is an accepted marker of brain atrophy. In this study, the approach of synthetic tissue mapping was applied, in which brain parenchymal fraction was automatically calculated based on absolute quantification of the tissue relaxation rates R1 and R2 and the proton attenuation. MATERIALS AND METHODS: The BPF values of 99 patients with MS and 35 control subjects were determined by using SyMap and tested in relationship to clinical variables. A subset of 5 patients with MS and 5 control subjects were also analyzed with a manual segmentation technique as a reference. Reproducibility of SyMap was assessed in a separate group of 6 healthy subjects, each scanned 6 consecutive times. RESULTS: Patients with MS had significantly lower BPF (0.852 0.0041, mean +/- SE) compared with control subjects (0.890 +/- 0.0040). Significant linear relationships between BPF and age, disease duration, and Expanded Disability Status Scale scores were observed (P < .001). A strong correlation existed between SyMap and the reference method (r = 0.96; P < .001) with no significant difference in mean BPF. Coefficient of variation of repeated SyMap BPF measurements was 0.45%. Scan time was <6 minutes, and postprocessing time was <2 minutes. CONCLUSIONS: SyMap is a valid and reproducible method for determining BPF in MS within a clinically acceptable scan time and postprocessing time. Results are highly congruent with those described using other methods and show high agreement with the manual reference method.

  • 35.
    Vågberg, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Norgren, Niklas
    UmanDiagnostics AB, Umeå, Sweden.
    Dring, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lindqvist, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Zetterberg, Henrik
    Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London, United Kingdom.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Levels and Age Dependency of Neurofilament Light and Glial Fibrillary Acidic Protein in Healthy Individuals and Their Relation to the Brain Parenchymal Fraction2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 8, artikel-id e0135886Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Neurofilament light (NFL) and Glial Fibrillary Acidic Protein (GFAP) are integral parts of the axonal and astrocytal cytoskeletons respectively and are released into the cerebrospinal fluid (CSF) in cases of cellular damage. In order to interpret the levels of these biomarkers in disease states, knowledge on normal levels in the healthy is required. Another biomarker for neurodegeneration is brain atrophy, commonly measured as brain parenchymal fraction (BPF) using magnetic resonance imaging (MRI). Potential correlations between levels of NFL, GFAP and BPF in healthy individuals have not been investigated. Objectives To present levels of NFL and GFAP in healthy individuals stratified for age, and investigate the correlation between them as well as their correlation with BPF. Methods The CSF was analysed in 53 healthy volunteers aged 21 to 70 (1 sample missing for GFAP analysis) and 48 of the volunteers underwent determination of BPF using MRI. Results Mean (+/- SD) NFL was 355 ng/L (+/- 214), mean GFAP was 421 ng/L (+/- 129) and mean BPF was 0.867 (+/- 0.035). All three biomarkers correlated with age. NFL also correlated with both GFAP and BPF. When controlled for age, only the correlation between NFL and GFAP retained statistical significance. Conclusions This study presents data on age-stratified levels of NFL and GFAP in the CSF of healthy individuals. There is a correlation between levels of NFL and GFAP and both increase with age. A correlation between NFL and BPF was also found, but did not retain statistical significance if controlled for age.

  • 36.
    Wåhlin, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Alperin, Noam
    Department of Radiology, University of Miami, Miami, Florida.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Assessment of craniospinal pressure-volume indices2010Ingår i: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 31, nr 9, s. 1645-1650Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND PURPOSE: The PVI(CC) of the craniospinal compartment defines the shape of the pressure-volume curve and determines the damping of cyclic arterial pulsations. Despite no reports of direct measurements of the PVI(CC) among healthy elderly, it is believed that a change away from adequate accommodation of cardiac-related pulsations may be a pathophysiologic mechanism seen in neurodegenerative disorders such as Alzheimer disease and idiopathic normal pressure hydrocephalus. In this study, blood and CSF flow measurements are combined with lumbar CSF infusion measurements to assess the craniospinal PVI(CC) and its distribution of cranial and spinal compartments in healthy elderly.

    MATERIALS AND METHODS: Thirty-seven healthy elderly were included (60-82 years of age). The cyclic arterial volume change and the resulting shift of CSF to the spinal compartment were quantified by PC-MR imaging. In addition, each subject underwent a lumbar CSF infusion test in which the magnitude of cardiac-related pulsations in intracranial pressure was quantified. Finally, the PVI was calculated by using a mathematic model.

    RESULTS: After excluding 2 extreme values, the craniospinal PVI(CC) was calculated to a mean of 9.8 ± 2.7 mL and the estimated average 95% confidence interval of individual measurements was ± 9%. The average intracranial and spinal contributions to the overall compliance were 65% and 35% respectively (n = 35).

    CONCLUSIONS: Combining lumbar CSF infusion and PC-MR imaging proved feasible and robust for assessment of the craniospinal PVI(CC). This study produced normative values and showed that the major compensatory contribution was located intracranially.

  • 37.
    Wåhlin, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    In healthy elderly the volumes of several brain regions are related to pulsatility in cerebral arteries and cerebrospinal fluidManuskript (preprint) (Övrigt vetenskapligt)
  • 38.
    Wåhlin, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Intracranial pulsatility is associated with regional brain volume in elderly individuals2014Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 35, nr 2, s. 365-372Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Excessive intracranial pulsatility is thought to damage the cerebral microcirculation, causing cognitive decline in elderly individuals. We investigated relationships between brain structure and measures related to intracranial pulsatility among healthy elderly. Thirty-seven stroke-free, non-demented individuals (62-82 years of age) were included. We assessed brain structure, invasively measured cerebrospinal fluid (CSF) pulse pressure, and magnetic resonance-quantified arterial and CSF flow pulsatility, as well as arterial pulse pressure. Using both multivariate partial least squares and ordinary regression analyses, we identified a significant pattern of negative relationships between the volume of several brain regions and measures of intracranial pulsatility. The strongest relationships concerned the temporal lobe cortex and hippocampus. These findings were also coherent with observations of positive relationships between intracranial pulsatility and ventricular volume. In conclusion, elderly subjects with high intracranial pulsatility display smaller brain volume and larger ventricles, supporting the notion that excessive cerebral arterial pulsatility harms the brain. This calls for research investigating altered intracranial cardiac-related pulsatile stress as a potential risk factor that may cause or worsen the prognosis in subjects developing cognitive impairment and dementia.

  • 39.
    Wåhlin, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Wieben, O
    Johnson, KM
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Measuring pulsatile flow in cerebral arteries using 4D phase-contrast magnetic resonance imaging2013Ingår i: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 34, nr 9, s. 1740-1745Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    BACKGROUND AND PURPOSE: 4D PCMRI can be used to quantify pulsatile hemodynamics in multiple cerebral arteries. The aim of this study was to compare 4D PCMRI and 2D PCMRI for assessments of pulsatile hemodynamics in major cerebral arteries. MATERIALS AND METHODS: We scanned the internal carotid artery, the anterior cerebral artery, the basilar artery, and the middle cerebral artery in 10 subjects with a single 4D and multiple 2D PCMRI acquisitions by use of a 3T system and a 32-channel head coil. We assessed the agreement regarding net flow and the volume of arterial pulsatility (V) for all vessels. RESULTS: 2D and 4D PCMRI produced highly correlated results, with r = 0.86 and r = 0.95 for V and net flow, respectively (n = 69 vessels). These values increased to r = 0.93 and r = 0.97, respectively, during investigation of a subset of measurements with <5% variation in heart rate between the 4D and 2D acquisition (n = 31 vessels). Significant differences were found for ICA and MCA net flow (P = .004 and P < .001, respectively) and MCA V (P = .006). However, these differences were attenuated and no longer significant when the subset with stable heart rate (n = 31 vessels) was analyzed. CONCLUSIONS: 4D PCMRI provides a powerful methodology to measure pulsatility of the larger cerebral arteries from a single acquisition. A large part of differences between measurements was attributed to physiologic variations. The results were consistent with 2D PCMRI.

  • 40.
    Wåhlin, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hauksson, Jón
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Phase contrast MRI quantification of pulsatile volumes of brain arteries, veins, and cerebrospinal fluids compartments: repeatability and physiological interactions2012Ingår i: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 35, nr 5, s. 1055-1062Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To study measurement repeatability and physiological determinants on measurement stability for phase contrast MRI (PC-MRI) measurements of cyclic volume changes (ΔV) of brain arteries, veins, and cerebrospinal fluid (CSF) compartments.

    MATERIALS AND METHODS: Total cerebral blood flow (tCBF), total internal jugular flow (tJBF) and spinal CSF flow at C2-C3 level and CSF in the aqueduct was measured using five repetitions in 20 healthy subjects. After subtracting net flow, waveforms were integrated to calculate ΔV of arterial, venous, and cerebrospinal fluid compartments. The intraclass correlation coefficient (ICC) was used to measure repeatability. Systematic errors were investigated by a series of phantom measurements.

    RESULTS: For ΔV calculated from tCBF, tJBF and both CSF waveforms, the ICC was ≥0.85. ΔV from the tCBF waveform decreased linearly between repetitions (P = 0.012). Summed CSF and venous volume being shifted out from the cranium was correlated with ΔV calculated from the tCBF waveform (r = 0.75; P < 0.001). Systematic errors increased at resolutions <4 pixels per diameter.

    CONCLUSION: Repeatability of ΔV calculated from tCBF, tJBF, and CSF waveforms allows useful interpretations. The subject's time in the MR system and imaging resolution should be considered when interpreting volume changes. Summed CSF and venous volume changes was associated with arterial volume changes.

    J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.

  • 41.
    Zarrinkoob, Laleh
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Ambarki, Khalid
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Aging alters the dampening of pulsatile blood flow in cerebral arteries2016Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 36, nr 9, s. 1519-1527Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Excessive pulsatile flow caused by aortic stiffness is thought to be a contributing factor for several cerebrovascular diseases. The main purpose of this study was to describe the dampening of the pulsatile flow from the proximal to the distal cerebral arteries, the effect of aging and sex, and its correlation to aortic stiffness. Forty-five healthy elderly (mean age 71 years) and 49 healthy young (mean age 25 years) were included. Phase-contrast magnetic resonance imaging was used for measuring blood flow pulsatility index and dampening factor (proximal artery pulsatility index/distal artery pulsatility index) in 21 cerebral and extra-cerebral arteries. Aortic stiffness was measured as aortic pulse wave velocity. Cerebral arterial pulsatility index increased due to aging and this was more pronounced in distal segments of cerebral arteries. There was no difference in pulsatility index between women and men. Dampening of pulsatility index was observed in all cerebral arteries in both age groups but was significantly higher in young subjects than in elderly. Pulse wave velocity was not correlated with cerebral arterial pulsatility index. The increased pulsatile flow in elderly together with reduced dampening supports the pulse wave encephalopathy theory, since it implies that a higher pulsatile flow is reaching distal arterial segments in older subjects.

  • 42.
    Zarrinkoob, Laleh
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Blood flow distribution in cerebral arteries2015Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 35, nr 4, s. 648-654Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High-resolution phase-contrast magnetic resonance imaging can now assess flow in proximal and distal cerebral arteries. The aim of this study was to describe how total cerebral blood flow (tCBF) is distributed into the vascular tree with regard to age, sex and anatomic variations. Forty-nine healthy young (mean 25 years) and 45 elderly (mean 71 years) individuals were included. Blood flow rate (BFR) in 21 intra-and extracerebral arteries was measured. Total cerebral blood flow was defined as BFR in the internal carotid plus vertebral arteries and mean cerebral perfusion as tCBF/brain volume. Carotid/vertebral distribution was 72%/28% and was not related to age, sex, or brain volume. Total cerebral blood flow (717 +/- 123 mL/min) was distributed to each side as follows: middle cerebral artery (MCA), 21%; distal MCA, 6%; anterior cerebral artery (ACA), 12%, distal ACA, 4%; ophthalmic artery, 2%; posterior cerebral artery (PCA), 8%; and 20% to basilar artery. Deviating distributions were observed in subjects with 'fetal' PCA. Blood flow rate in cerebral arteries decreased with increasing age (P < 0.05) but not in extracerebral arteries. Mean cerebral perfusion was higher in women (women: 61 +/- 8; men: 55 +/- 6 mL/min/100 mL, P < 0.001). The study describes a new method to outline the flow profile of the cerebral vascular tree, including reference values, and should be used for grading the collateral flow system.

  • 43.
    Zarrinkoob, Laleh
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Blood flow lateralization and collateral compensatory mechanisms in patients with carotid artery stenosis2019Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 50, nr 5, s. 1081-1088Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Purpose: Four-dimensional phase-contrast magnetic resonance imaging enables quantification of blood flow rate (BFR; mL/min) in multiple cerebral arteries simultaneously, making it a promising technique for hemodynamic investigation in patients with stroke. The aim of this study was to quantify the hemodynamic disturbance and the compensatory pattern of collateral flow in patients with symptomatic carotid stenosis.

    Methods: Thirty-eight patients (mean, 72 years; 27 men) with symptomatic carotid stenosis (>/=50%) or occlusion were investigated using 4-dimensional phase-contrast magnetic resonance imaging. For each patient, BFR was measured in 19 arteries/locations. The ipsilateral side to the symptomatic carotid stenosis was compared with the contralateral side.

    Results: Internal carotid artery BFR was lower on the ipsilateral side (134+/-87 versus 261+/-95 mL/min; P<0.001). BFR in anterior cerebral artery (A1 segment) was lower on ipsilateral side (35+/-58 versus 119+/-72 mL/min; P<0.001). Anterior cerebral artery territory bilaterally was primarily supplied by contralateral internal carotid artery. The ipsilateral internal carotid artery mainly supplied the ipsilateral middle cerebral artery (MCA) territory. MCA was also supplied by a reversed BFR found in the ophthalmic and the posterior communicating artery routes on the ipsilateral side (-5+/-28 versus 10+/-28 mL/min, P=0.001, and -2+/-12 versus 6+/-6 mL/min, P=0.03, respectively). Despite these compensations, BFR in MCA was lower on the ipsilateral side, and this laterality was more pronounced in patients with severe carotid stenosis (>/=70%). Although comparing ipsilateral MCA BFR between stenosis groups (<70% and >/=70%), there was no difference ( P=0.95).

    Conclusions: With a novel approach using 4-dimensional phase-contrast magnetic resonance imaging, we could simultaneously quantify and rank the importance of collateral routes in patients with carotid stenosis. An important observation was that contralateral internal carotid artery mainly secured the bilateral anterior cerebral artery territory. Because of the collateral recruitment, compromised BFR in MCA is not necessarily related to the degree of carotid stenosis. These findings highlight the importance of simultaneous investigation of the hemodynamics of the entire cerebral arterial tree.

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