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Publications (7 of 7) Show all publications
Rivera-Rivera, L. A., Vikner, T., Eisenmenger, L., Johnson, S. C. & Johnson, K. M. (2023). Four-dimensional flow MRI for quantitative assessment of cerebrospinal fluid dynamics: Status and opportunities. NMR in Biomedicine, Article ID e5082.
Open this publication in new window or tab >>Four-dimensional flow MRI for quantitative assessment of cerebrospinal fluid dynamics: Status and opportunities
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2023 (English)In: NMR in Biomedicine, ISSN 0952-3480, E-ISSN 1099-1492, article id e5082Article in journal (Refereed) Epub ahead of print
Abstract [en]

Neurological disorders can manifest with altered neurofluid dynamics in different compartments of the central nervous system. These include alterations in cerebral blood flow, cerebrospinal fluid (CSF) flow, and tissue biomechanics. Noninvasive quantitative assessment of neurofluid flow and tissue motion is feasible with phase contrast magnetic resonance imaging (PC MRI). While two-dimensional (2D) PC MRI is routinely utilized in research and clinical settings to assess flow dynamics through a single imaging slice, comprehensive neurofluid dynamic assessment can be limited or impractical. Recently, four-dimensional (4D) flow MRI (or time-resolved three-dimensional PC with three-directional velocity encoding) has emerged as a powerful extension of 2D PC, allowing for large volumetric coverage of fluid velocities at high spatiotemporal resolution within clinically reasonable scan times. Yet, most 4D flow studies have focused on blood flow imaging. Characterizing CSF flow dynamics with 4D flow (i.e., 4D CSF flow) is of high interest to understand normal brain and spine physiology, but also to study neurological disorders such as dysfunctional brain metabolite waste clearance, where CSF dynamics appear to play an important role. However, 4D CSF flow imaging is challenged by the long T1 time of CSF and slower velocities compared with blood flow, which can result in longer scan times from low flip angles and extended motion-sensitive gradients, hindering clinical adoption. In this work, we review the state of 4D CSF flow MRI including challenges, novel solutions from current research and ongoing needs, examples of clinical and research applications, and discuss an outlook on the future of 4D CSF flow.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
4D flow, CSF, dynamics, motion, MRI, phase contrast, Venc
National Category
Medical Image Processing Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-218889 (URN)10.1002/nbm.5082 (DOI)2-s2.0-85180243828 (Scopus ID)
Funder
NIH (National Institutes of Health), UL1TR002373, KL2TR002374, R21NS125094, R21AG077337, P30AG062715, R01AG021155, R01AG027161, R01AG075788
Available from: 2024-01-04 Created: 2024-01-04 Last updated: 2024-01-04
Vikner, T., Karalija, N., Eklund, A., Malm, J., Lundquist, A., Gallewicz, N., . . . Wåhlin, A. (2022). 5-year associations among cerebral arterial pulsatility, perivascular space dilation, and white matter lesions. Annals of Neurology, 92(5), 871-881
Open this publication in new window or tab >>5-year associations among cerebral arterial pulsatility, perivascular space dilation, and white matter lesions
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2022 (English)In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 92, no 5, p. 871-881Article in journal (Refereed) Published
Abstract [en]

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

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

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

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

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-199208 (URN)10.1002/ana.26475 (DOI)000843724700001 ()36054261 (PubMedID)2-s2.0-85136905097 (Scopus ID)
Funder
Swedish Foundation for Strategic ResearchRegion Västerbotten, 2017‐04949Knut and Alice Wallenberg Foundation, 2017‐04949Max Planck SocietySwedish Research Council, 2017‐02217Swedish Research Council, 421‐2012‐648
Available from: 2022-09-08 Created: 2022-09-08 Last updated: 2023-05-04Bibliographically approved
Vikner, T. (2022). Cerebral arterial pulsatility imaging using 4D flow MRI: methodological development and applications in brain aging. (Doctoral dissertation). Umeå: Umeå University
Open this publication in new window or tab >>Cerebral arterial pulsatility imaging using 4D flow MRI: methodological development and applications in brain aging
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

4D flow magnetic resonance imaging (MRI) is increasingly recognizedas a versatile tool to assess arterial and venous hemodynamics. Cerebral arterial pulsatility is typically assessed by analyzing flow waveforms over the cardiac cycle, where flow amplitude is a function of cardiac output, central arterial stiffness, and cerebrovascular resistance and compliance. Excessive pulsatility may propagate to the cerebral microcirculation, and constitute a harmful mechanism for the brain. Indeed, imaging studies have linked arterial pulsatility to hippocampus volume, cerebral small vessel disease (SVD), and Alzheimer’s disease (AD). In animal models, elevated pulsatility leads to blood-brain barrier (BBB) leakage, capillary loss, and cognitive decline. However, associations to cerebrovascular lesions and brain function in the spectrum of normal aging are less investigated. Further, previous 4D flow studies have mainly assessed pulsatility in relatively large cerebral arteries. When exploring links to microvascular damage and brain function, more distal measurements, closer to the microcirculation, are desired. 

This thesis aimed to develop 4D flow MRI post-processing methods to obtain pulsatile waveforms in small, distal cerebral arteries with noisy velocity data and a complex vascular anatomy, and to evaluate pulsatility (primarily assessed by the pulsatility index) in relation to aging, brain function, and other imaging biomarkers of cerebrovascular damage, with particular dedication towards the hippocampus and cerebral SVD. 

To assess pulsatility in distal cerebral arteries, a post-processing method that automatically samples waveforms from numerous small arteries, to obtain a whole-brain representation of the distal arterial waveform, was developed (Paper I). We demonstrated the importance of averaging flow waveforms along multiple vessel segments to avoid overestimations in the pulsatility index, showed agreement with reference methods, and linked distal arterial pulsatility to age. 

To explore links to hippocampal function, we evaluated pulsatility in relation to cognition, hemodynamic low-frequency oscillations (LFOs), perfusion, and hippocampus volume (Paper II). We found that higher pulsatility was linked to worse hippocampus-sensitive episodic memory, weaker hippocampal LFOs, and lower whole-brain perfusion. These findings aligned with models suggesting that hippocampal microvessels could be particularly susceptible to pulsatile stress.

To inform on SVD pathophysiology, we evaluated 5-year associations among pulsatility, white matter lesions (WMLs) and perivascular space (PVS) dilation, using mixed models, factor analysis, and change score models (Paper III). Lead-lag analyses indicated that, while pulsatility at baseline could not predict WML nor PVS progression, WML and PVS volumes at baseline predicted 5-year pulsatility-increases. These findings indicate that individuals with a higher load of cerebrovascular damage are more prone to see increased pulsatility over time, and suggest that high pulsatility is a manifestation, rather a risk factor, for cerebral SVD.   

To shed light on the potential role of BBB leakage in aging and SVD, we used dynamic contrast enhanced (DCE) MRI and intravenous gadolinium injections to quantify BBB permeability (Paper IV). We found stepwise increases in permeability from healthy white matter to WMLs, supporting that BBB leakages are implicated in SVD. However, hippocampal BBB permeability was unrelated to age, indicating that this capillary property is maintained in aging. Finally, arterial pulsatility was unrelated to BBB permeability in WMLs and in the hippocampus, providing no evidence of excessive pulsatility as a trigger of BBB leakage. 

In conclusion, distal arterial pulsatility measurements are reliable when averaging 4D flow waveforms over a large number of vessels. Pulsatility increases with age, and individuals with more cerebrovascular lesions are prone to see larger increases over time. Pulsatility is negatively related to perfusion and hippocampal function. However, the temporal dynamics among the SVD biomarkers, and the absence of pulsatility–permeability associations, challenge the concept of excessive pulsatility as a trigger of microvascular damage. Future studies are needed to understand whether altered cerebral hemodynamics play a causal role in cognitive decline and dementia. Meanwhile, 4D flow hemodynamic parameters could be useful as biomarkers related to vessel properties and cerebrovascular health. 

Place, publisher, year, edition, pages
Umeå: Umeå University, 2022. p. 78
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2209
Keywords
Magnetic resonance imaging, 4D flow MRI, medical image analysis, cerebral hemodynamics, arterial pulsatility, DCE MRI, blood-brain barrier, white matter lesions, perivascular spaces, cerebral small vessel disease, hippocampus, cognition, aging
National Category
Neurology Neurosciences
Research subject
Biomedical Radiation Science
Identifiers
urn:nbn:se:umu:diva-200458 (URN)978-91-7855-924-4 (ISBN)978-91-7855-925-1 (ISBN)
Public defence
2022-11-18, Föreläsningssal A5, Målpunkt R04, Rum 6A5, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Note

Ny lokal för disputationen. 

New location for disputation. 

Available from: 2022-10-28 Created: 2022-10-20 Last updated: 2022-11-08Bibliographically approved
Nyberg, L., Karalija, N., Papenberg, G., Salami, A., Andersson, M., Pedersen, R., . . . Bäckman, L. (2022). Longitudinal stability in working memory and frontal activity in relation to general brain maintenance. Scientific Reports, 12(1), Article ID 20957.
Open this publication in new window or tab >>Longitudinal stability in working memory and frontal activity in relation to general brain maintenance
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2022 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 20957Article in journal (Refereed) Published
Abstract [en]

Cognitive functions are well-preserved for some older individuals, but the underlying brain mechanisms remain disputed. Here, 5-year longitudinal 3-back in-scanner and offline data classified individuals in a healthy older sample (baseline age = 64–68 years) into having stable or declining working-memory (WM). Consistent with a vital role of the prefrontal cortex (PFC), WM stability or decline was related to maintained or reduced longitudinal PFC functional responses. Subsequent analyses of imaging markers of general brain maintenance revealed higher levels in the stable WM group on measures of neurotransmission and vascular health. Also, categorical and continuous analyses showed that rate of WM decline was related to global (ventricles) and local (hippocampus) measures of neuronal integrity. Thus, our findings support a role of the PFC as well as general brain maintenance in explaining heterogeneity in longitudinal WM trajectories in aging.

Place, publisher, year, edition, pages
Springer Nature, 2022
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-201756 (URN)10.1038/s41598-022-25503-9 (DOI)000984275000060 ()36470934 (PubMedID)2-s2.0-85143310050 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council, 2018-05973Umeå UniversityRegion VästerbottenThe Swedish Brain Foundation
Note

The freesurfer-analyses were performed on resources provided by the Swedish National Infrastructure for Computing (SNIC) at HPC2N, Umeå University

Available from: 2022-12-21 Created: 2022-12-21 Last updated: 2023-09-05Bibliographically approved
Vikner, T., Eklund, A., Karalija, N., Malm, J., Riklund, K., Lindenberger, U., . . . Wåhlin, A. (2021). Cerebral arterial pulsatility is linked to hippocampal microvascular function and episodic memory in healthy older adults. Journal of Cerebral Blood Flow and Metabolism, 41(7), 1778-1790
Open this publication in new window or tab >>Cerebral arterial pulsatility is linked to hippocampal microvascular function and episodic memory in healthy older adults
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2021 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 41, no 7, p. 1778-1790Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Sage Publications, 2021
Keywords
4D flow MRI, arterial stiffness, hippocampus, cognition, vasomotion
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-184408 (URN)10.1177/0271678X20980652 (DOI)000664214100024 ()33444091 (PubMedID)2-s2.0-85099415705 (Scopus ID)
Available from: 2021-06-14 Created: 2021-06-14 Last updated: 2023-03-07Bibliographically approved
Vikner, T., Nyberg, L., Holmgren, M., Malm, J., Eklund, A. & Wåhlin, A. (2020). Characterizing pulsatility in distal cerebral arteries using 4D flow MRI. Journal of Cerebral Blood Flow and Metabolism, 40(12), 2429-2440
Open this publication in new window or tab >>Characterizing pulsatility in distal cerebral arteries using 4D flow MRI
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2020 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 40, no 12, p. 2429-2440Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Sage Publications, 2020
Keywords
4D flow MRI, cerebral hemodynamics, arterial pulsatility, cerebral cortical arteries, aging
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-166582 (URN)10.1177/0271678X19886667 (DOI)000497309400001 ()31722598 (PubMedID)2-s2.0-85075164443 (Scopus ID)
Funder
Swedish Research Council, 2015-05616Swedish Research Council, 2017-04949
Available from: 2019-12-20 Created: 2019-12-20 Last updated: 2023-03-24Bibliographically approved
Vikner, T., Garpebring, A., Björnfot, C., Nyberg, L., Malm, J., Eklund, A. & Wåhlin, A.Blood-brain barrier permeability, vascular density, and cerebral 4D flow MRI hemodynamics in a population-based elderly cohort.
Open this publication in new window or tab >>Blood-brain barrier permeability, vascular density, and cerebral 4D flow MRI hemodynamics in a population-based elderly cohort
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(English)Manuscript (preprint) (Other academic)
Keywords
Magnetic resonance imaging, 4D flow MRI, DCE MRI, cerebral, hemodynamics, arterial pulsatility, blood-brain barrier permeability, vascular density, white matter lesions, hippocampus
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-200456 (URN)
Available from: 2022-10-20 Created: 2022-10-20 Last updated: 2023-09-14
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-3181-785X

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