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  • 1. Alakurtti, Kati
    et al.
    Johansson, Jarkko J.
    Joutsa, Juho
    Laine, Matti
    Backman, Lars
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Rinne, Juha O.
    Long-term test-retest reliability of striatal and extrastriatal dopamine D-2/3 receptor binding: study with [C-11]raclopride and high-resolution PET2015Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 35, nr 7, s. 1199-1205Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We measured the long-term test-retest reliability of [C-11]raclopride binding in striatal subregions, the thalamus and the cortex using the bolus-plus-infusion method and a high-resolution positron emission scanner. Seven healthy male volunteers underwent two positron emission tomography (PET) [C-11]raclopride assessments, with a 5-week retest interval. D-2/3 receptor availability was quantified as binding potential using the simplified reference tissue model. Absolute variability (VAR) and intraclass correlation coefficient (ICC) values indicated very good reproducibility for the striatum and were 4.5%/0.82, 3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum, respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC of 0.92. Test-retest data for cortical areas showed good to moderate reproducibility (6.1% to 13.1%). Our results are in line with previous test-retest studies of [C-11]raclopride binding in the striatum. A novel finding is the relatively low variability of [C-11]raclopride binding, providing suggestive evidence that extrastriatal D-2/3 binding can be studied in vivo with [C-11]raclopride PET to be verified in future studies.

  • 2.
    Björnfot, Cecilia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Larsson, Jenny
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Hansson, William
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Birnefeld, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Garpebring, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults: a 4D flow MRI study2024Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 3.
    Björnfot, Cecilia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Garpebring, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wahlin, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Assessing cerebral arterial pulse wave velocity using 4D flow MRI2021Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 41, nr 10, s. 2769-2777Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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  • 4. Hicks, Justin
    et al.
    Sadovski, Oleg
    Parkes, Jun
    Fowler, Chris
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Houle, Sylvain
    Tong, Junchao
    Vasdev, Neil
    Wilson, Alan
    Evaluation of a small library of carbamates and ureas, including PF-04457845, as potential imaging agents for fatty acid amide hydrolase (FAAH)2012Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 32, s. S17-S17Artikel i tidskrift (Övrigt vetenskapligt)
  • 5.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jugular vein collapse in upright and its relation to intracranial pressure regulation2017Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, s. 297-297Artikel i tidskrift (Refereegranskat)
  • 6.
    Jiang, Wei
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Gu, Weigang
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Hossmann, Konstantin-Alexander
    Mies, Günter
    Wester, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Establishing a photothrombotic 'ring' stroke model in adult mice with late spontaneous reperfusion: quantitative measurements of cerebral blood flow and cerebral protein synthesis.2006Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 26, nr 7, s. 927-936Artikel i tidskrift (Refereegranskat)
  • 7.
    Johansson, Jarkko
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Ericsson, Madelene
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    af Bjerkén, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Virel, Ana
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Karalija, Nina
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Amphetamine-induced dopamine release in rat: Whole-brain spatiotemporal analysis with [11C]raclopride and positron emission tomography2023Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Whole-brain mapping of drug effects are needed to understand the neural underpinnings of drug-related behaviors. Amphetamine administration is associated with robust increases in striatal dopamine (DA) release. Dopaminergic terminals are, however, present across several associative brain regions, which may contribute to behavioral effects of amphetamine. Yet the assessment of DA release has been restricted to a few brain regions of interest. The present work employed positron emission tomography (PET) with [11C]raclopride to investigate regional and temporal characteristics of amphetamine-induced DA release across twenty sessions in adult female Sprague Dawley rats. Amphetamine was injected intravenously (2 mg/kg) to cause displacement of [11C]raclopride binding from DA D2-like receptors, assessed using temporally sensitive pharmacokinetic PET model (lp-ntPET). We show amphetamine-induced [11C]raclopride displacement in the basal ganglia, and no changes following saline injections. Peak occupancy was highest in nucleus accumbens, followed by caudate-putamen and globus pallidus. Importantly, significant amphetamine-induced displacement was also observed in several extrastriatal regions, and specifically in thalamus, insula, orbitofrontal cortex, and secondary somatosensory area. For these, peak occupancy occurred later and was lower as compared to the striatum. Collectively, these findings demonstrate distinct amphetamine-induced DA responses across the brain, and that [11C]raclopride-PET can be employed to detect such spatiotemporal differences.

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  • 8.
    Jonasson, My
    et al.
    Department of Surgical Sciences, Nuclear Medicine and PET, Uppsala University, Uppsala, Sweden; Medical Physics, Uppsala University Hospital, Uppsala, Sweden.
    Frick, Andreas
    Department of Medical Sciences, Psychiatry, Uppsala University, Uppsala, Sweden.
    Fazio, Patrik
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Hjorth, Olof
    Department of Psychology, Uppsala University, Uppsala, Sweden.
    Danfors, Torsten
    Department of Surgical Sciences, Nuclear Medicine and PET, Uppsala University, Uppsala, Sweden; Medical Imaging Centre, Uppsala University Hospital, Uppsala, Sweden.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Appel, Lieuwe
    Department of Surgical Sciences, Nuclear Medicine and PET, Uppsala University, Uppsala, Sweden; Medical Imaging Centre, Uppsala University Hospital, Uppsala, Sweden.
    Furmark, Tomas
    Department of Psychology, Uppsala University, Uppsala, Sweden.
    Varrone, Andrea
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Lubberink, Mark
    Department of Surgical Sciences, Nuclear Medicine and PET, Uppsala University, Uppsala, Sweden; Medical Physics, Uppsala University Hospital, Uppsala, Sweden.
    Striatal dopamine transporter and receptor availability correlate with relative cerebral blood flow measured with [11C]PE2I, [18F]FE-PE2I and [11C]raclopride PET in healthy individuals2023Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 43, nr 7, s. 1206-1215Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this retrospective study was to investigate relationships between relative cerebral blood flow and striatal dopamine transporter and dopamine D2/3 availability in healthy subjects. The data comprised dynamic PET scans with two dopamine transporter tracers [11C]PE2I (n = 20) and [18F]FE-PE2I (n = 20) and the D2/3 tracer [11C]raclopride (n = 18). Subjects with a [11C]PE2I scan also underwent a dynamic scan with the serotonin transporter tracer [11C]DASB. Binding potential (BPND) and relative tracer delivery (R1) values were calculated on regional and voxel-level. Striatal R1 and BPND values were correlated, using either an MRI-based volume of interest (VOI) or an isocontour VOI based on the parametric BPND image. An inter-tracer comparison between [11C]PE2I BPND and [11C]DASB R1 was done on a VOI-level and simulations were performed to investigate whether the constraints of the modeling could cause correlation of the parameters. A positive association was found between BPND and R1 for all three dopamine tracers. A similar correlation was found for the inter-tracer correlation between [11C]PE2I BPND and [11C]DASB R1. Simulations showed that this relationship was not caused by cross-correlation between parameters in the kinetic model. In conclusion, these results suggest an association between resting-state striatal dopamine function and relative blood flow in healthy subjects.

  • 9.
    Karalija, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Jonasson, Lars S.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Johansson, Jarkko
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Papenberg, Goran
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Karolinska Institutet; Stockholm University.
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Copenhagen University Hospital, Hvidovre, Denmark.
    High long-term test-retest reliability for extrastriatal 11C-raclopride binding in healthy older adults2020Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 40, nr 9, s. 1859-1868Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In vivo dopamine D2-receptor availability is frequently assessed with 11C-raclopride and positron emission tomography. Due to low signal-to-noise ratios for 11C-raclopride in areas with low D2 receptor densities, the ligand has been considered unreliable for measurements outside the dopamine-dense striatum. Intriguingly, recent studies show that extrastriatal 11C-raclopride binding potential (BPND) values are (i) reliably higher than in the cerebellum (where D2-receptor levels are negligible), (ii) correlate with behavior in the expected direction, and (iii) showed good test-retest reliability in a sample of younger adults. The present work demonstrates high seven-month test-retest reliability of striatal and extrastriatal 11C-raclopride BPND values in healthy, older adults (n = 27, age: 64-78 years). Mean 11C-raclopride BPND values were stable between test sessions in subcortical nuclei, and in frontal and temporal cortices (p > 0.05). Across all structures analyzed, intraclass correlation coefficients were high (0.85-0.96), absolute variability was low (mean: 4-8%), and coefficients of variance ranged between 9 and 25%. Furthermore, regional 11C-raclopride BPND values correlated with previously determined 18F-fallypride BPND values (rho = 0.97 and 0.92 in correlations with and without striatal values, respectively, p < 0.01) and postmortem determined D2-receptor densities (including striatum: rho = 0.92; p < 0.001; excluding striatum: rho = 0.75; p = 0.067). These observations suggest that extrastriatal 11C-raclopride measurements represent a true D2 signal.

  • 10.
    Kuttner, Samuel
    et al.
    Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Department of Physics and Technology, UiT The Arctic University of Norway, Tromsø, Norway; The PET Imaging Center, University Hospital of North Norway, Tromsø, Norway.
    Wickstrøm, Kristoffer Knutsen
    Department of Physics and Technology, UiT The Arctic University of Norway, Tromsø, Norway.
    Lubberink, Mark
    Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
    Tolf, Andreas
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, Joachim
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Sundset, Rune
    Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; The PET Imaging Center, University Hospital of North Norway, Tromsø, Norway.
    Jenssen, Robert
    Department of Physics and Technology, UiT The Arctic University of Norway, Tromsø, Norway.
    Appel, Lieuwe
    Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Cerebral blood flow measurements with 15O-water PET using a non-invasive machine-learning-derived arterial input function2021Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 41, nr 9, s. 2229-2241Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cerebral blood flow (CBF) can be measured with dynamic positron emission tomography (PET) of 15O-labeled water by using tracer kinetic modelling. However, for quantification of regional CBF, an arterial input function (AIF), obtained from arterial blood sampling, is required. In this work we evaluated a novel, non-invasive approach for input function prediction based on machine learning (MLIF), against AIF for CBF PET measurements in human subjects. Twenty-five subjects underwent two 10 min dynamic 15O-water brain PET scans with continuous arterial blood sampling, before (baseline) and following acetazolamide medication. Three different image-derived time-activity curves were automatically segmented from the carotid arteries and used as input into a Gaussian process-based AIF prediction model, considering both baseline and acetazolamide scans as training data. The MLIF approach was evaluated by comparing AIF and MLIF curves, as well as whole-brain grey matter CBF values estimated by kinetic modelling derived with either AIF or MLIF.

    The results showed that AIF and MLIF curves were similar and that corresponding CBF values were highly correlated and successfully differentiated before and after acetazolamide medication. In conclusion, our non-invasive MLIF method shows potential to replace the AIF obtained from blood sampling for CBF measurements using 15O-water PET and kinetic modelling.

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  • 11.
    Vikner, Tomas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Karalija, Nina
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Lindenberger, Ulman
    Bäckman, Lars
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Cerebral arterial pulsatility is linked to hippocampal microvascular function and episodic memory in healthy older adults2021Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 41, nr 7, s. 1778-1790Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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  • 12.
    Vikner, Tomas
    et al.
    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). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Holmgren, Madelene
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Characterizing pulsatility in distal cerebral arteries using 4D flow MRI2020Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 40, nr 12, s. 2429-2440Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 13.
    Virhammar, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Laurell, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ahlgren, Andre
    Department of Medical Radiation Physics, Lund University.
    Cesarini, Kristina Giuliana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Idiopathic normal pressure hydrocephalus: cerebral perfusion measured with pCASL before and repeatedly after CSF removal2014Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 34, nr 11, s. 1771-1778Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pseudo-continuous arterial, spin labeling (pCASL) measurements were performed in 20 patients with idiopathic normal pressure hydrocephalus (iNPH) to investigate whether cerebral blood flow (CBF) increases during the first 24 hours after a cerebrospinal fluid tap test (CSF TT). Five pCASL magnetic resonance imaging (MRI) scans were performed. Two scans were performed before removal of 40 mL CSF, and the other three at 30 minutes, 4 hours, and 24 hours, respectively after the CSF TT. Thirteen different regions of interest (ROIs) were manually drawn on coregistered MR images. In patients with increased CBF in lateral and frontal white matter after the CSF TT, gait function improved more than it did in patients with decreased CBF in these regions. However, in the whole sample, there was no significant increase in CBF after CSF removal compared with baseline investigations. The repeatability of CBF measurements at baseline was high, with intraclass correlation coefficients of 0.60 to 0.90 for different ROIs, but the median regional variability was in the range of 5% to 17%. Our results indicate that CBF in white matter close to the lateral ventricles plays a role in the reversibility of symptoms after CSF removal in patients with iNPH.

  • 14.
    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.

  • 15.
    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.

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