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Mogensen, K., Guarrasi, V., Larsson, J., Hansson, W., Wåhlin, A., Koskinen, L.-O. D., . . . Qvarlander, S. (2025). An optimized ensemble search approach for classification of higher-level gait disorder using brain magnetic resonance images. Computers in Biology and Medicine, 184, Article ID 109457.
Open this publication in new window or tab >>An optimized ensemble search approach for classification of higher-level gait disorder using brain magnetic resonance images
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2025 (English)In: Computers in Biology and Medicine, ISSN 0010-4825, E-ISSN 1879-0534, Vol. 184, article id 109457Article in journal (Refereed) Published
Abstract [en]

Higher-Level Gait Disorder (HLGD) is a type of gait disorder estimated to affect up to 6% of the older population. By definition, its symptoms originate from the higher-level nervous system, yet its association with brain morphology remains unclear. This study hypothesizes that there are patterns in brain morphology linked to HLGD. For the first time in the literature, this work investigates whether deep learning, in the form of convolutional neural networks, can capture patterns in magnetic resonance images to identify individuals affected by HLGD. To handle this new classification task, we propose setting up an ensemble of models. This leverages the benefits of combining classifiers instead of determining which network is the most suitable, developing a new architecture, or customizing an existing one. We introduce a computationally cost-effective search algorithm to find the optimal ensemble by leveraging a cost function of both traditional performance scores and the diversity among the models. Using a unique dataset from a large population-based cohort (VESPR), the ensemble identified by our algorithm demonstrated superior performance compared to single networks, other ensemble fusion techniques, and the best linear radiological measure. This emphasizes the importance of implementing diversity into the cost function. Furthermore, the results indicate significant morphological differences in brain structure between HLGD-affected individuals and controls, motivating research about which areas the networks base their classifications on, to get a better understanding of the pathophysiology of HLGD.

Place, publisher, year, edition, pages
Elsevier, 2025
Keywords
Artificial intelligence, CNN, Convolutional neural networks, Ensemble learning, Gait disorder, Medical imaging, MRI, Neurological disorders, Normal pressure hydrocephalus, Optimization
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-232782 (URN)10.1016/j.compbiomed.2024.109457 (DOI)2-s2.0-85210376400 (Scopus ID)
Funder
Swedish Foundation for Strategic Research, RMX18-0152Swedish Research Council, 2021-00711_VR/JPNDUmeå UniversityRegion Västerbotten
Available from: 2024-12-13 Created: 2024-12-13 Last updated: 2024-12-13Bibliographically approved
Vikström, A., Eklund, A., Johannesdottir, M., Wåhlin, A., Zarrinkoob, L., Malm, J., . . . Holmlund, P. (2025). Non-invasive assessment of cerebral perfusion pressure: Applied towards preoperative planning of aortic arch surgery with selective antegrade cerebral perfusion. Journal of Biomechanics, 179, Article ID 112459.
Open this publication in new window or tab >>Non-invasive assessment of cerebral perfusion pressure: Applied towards preoperative planning of aortic arch surgery with selective antegrade cerebral perfusion
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2025 (English)In: Journal of Biomechanics, ISSN 0021-9290, E-ISSN 1873-2380, Vol. 179, article id 112459Article in journal (Refereed) Published
Abstract [en]

Selective antegrade cerebral perfusion (SACP) is a protective procedure to ascertain adequate brain perfusion during aortic arch surgeries requiring moderate hypothermic circulatory arrest. SACP entails catheterization of arteries feeding the brain, which can be done bilaterally (bSACP) or unilaterally (uSACP), but there is no consensus on when to use each approach. bSACP may increase the risk of embolization, while uSACP risks hypoperfusion due to insufficient perfusion pressure in the contralateral hemisphere, since a single catheter must perfuse both hemispheres. We developed and tested the feasibility of a new method for predicting cerebral perfusion pressures (CPP) during SACP, which could potentially aid clinicians in preoperatively identifying which SACP approach to use. Feasibility of the method was evaluated in five patients eligible for aortic arch surgery (65 ± 7 years, 3 men). Patients were investigated preoperatively with computed tomography angiography (CTA) and 4D flow magnetic resonance imaging (MRI) to assess patient-specific arterial anatomy and blood flows. From the imaging, computational fluid dynamics (CFD) simulations estimated the patients' vascular resistances. Applying these resistances and intraoperative SACP pressure/flow settings to the model's boundary conditions allowed for predictions of contralateral CPP during SACP. Predicted pressures were compared to corresponding intraoperative pressure measurements. The method showed promise for predicting contralateral CPP during both uSACP (median error (range): 2.4 (−0.2–18.0) mmHg) and bSACP (0.8 (−3.3–5.4) mmHg). Predictions were most sensitive to collateral artery size. This study showed the feasibility of CPP predictions of SACP, and presents key features needed for accurate modelling.

Place, publisher, year, edition, pages
Elsevier, 2025
Keywords
4D flow MRI, Aortic arch surgery, Cerebral perfusion pressure, Computational fluid dynamics, Selective antegrade cerebral perfusion
National Category
Surgery Physiology and Anatomy
Identifiers
urn:nbn:se:umu:diva-233313 (URN)10.1016/j.jbiomech.2024.112459 (DOI)001383269200001 ()39662261 (PubMedID)2-s2.0-85211374967 (Scopus ID)
Funder
Region Västerbotten
Available from: 2025-01-03 Created: 2025-01-03 Last updated: 2025-02-10Bibliographically approved
Vikner, T., Garpebring, A., Björnfot, C., Nyberg, L., Malm, J., Eklund, A. & Wåhlin, A. (2024). Blood-brain barrier integrity is linked to cognitive function, but not to cerebral arterial pulsatility, among elderly. Scientific Reports, 14(1), Article ID 15338.
Open this publication in new window or tab >>Blood-brain barrier integrity is linked to cognitive function, but not to cerebral arterial pulsatility, among elderly
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2024 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, no 1, article id 15338Article in journal (Refereed) Published
Abstract [en]

Blood-brain barrier (BBB) disruption may contribute to cognitive decline, but questions remain whether this association is more pronounced for certain brain regions, such as the hippocampus, or represents a whole-brain mechanism. Further, whether human BBB leakage is triggered by excessive vascular pulsatility, as suggested by animal studies, remains unknown. In a prospective cohort (N = 50; 68-84 years), we used contrast-enhanced MRI to estimate the permeability-surface area product (PS) and fractional plasma volume ( formula presented ), and 4D flow MRI to assess cerebral arterial pulsatility. Cognition was assessed by the Montreal Cognitive Assessment (MoCA) score. We hypothesized that high PS would be associated with high arterial pulsatility, and that links to cognition would be specific to hippocampal PS. For 15 brain regions, PS ranged from 0.38 to 0.85 (·10-3 min-1) and formula presented from 0.79 to 1.78%. Cognition was related to PS (·10-3 min-1) in hippocampus (β = - 2.9; p = 0.006), basal ganglia (β = - 2.3; p = 0.04), white matter (β = - 2.6; p = 0.04), whole-brain (β = - 2.7; p = 0.04) and borderline-related for cortex (β = - 2.7; p = 0.076). Pulsatility was unrelated to PS for all regions (p > 0.19). Our findings suggest PS-cognition links mainly reflect a whole-brain phenomenon with only slightly more pronounced links for the hippocampus, and provide no evidence of excessive pulsatility as a trigger of BBB disruption.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-227865 (URN)10.1038/s41598-024-65944-y (DOI)38961135 (PubMedID)2-s2.0-85197675960 (Scopus ID)
Funder
Swedish Research Council, 2022-04263Swedish Heart Lung Foundation, 20210653Swedish Foundation for Strategic ResearchThe Kempe Foundations
Available from: 2024-07-19 Created: 2024-07-19 Last updated: 2024-07-19Bibliographically approved
Björnfot, C., Eklund, A., Larsson, J., Hansson, W., Birnefeld, J., Garpebring, A., . . . Wåhlin, A. (2024). Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults: a 4D flow MRI study. Journal of Cerebral Blood Flow and Metabolism, 44(8), 1343-1351
Open this publication in new window or tab >>Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults: a 4D flow MRI study
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2024 (English)In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 44, no 8, p. 1343-1351Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Sage Publications, 2024
Keywords
4D flow MRI, cerebral small vessel disease, perivascular spaces, pulse wave velocity, white matter hyperintensities
National Category
Cardiology and Cardiovascular Disease Neurology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-221120 (URN)10.1177/0271678X241230741 (DOI)001157963000001 ()38315044 (PubMedID)2-s2.0-85184419786 (Scopus ID)
Funder
Swedish Foundation for Strategic Research, RMX18-0152Swedish Heart Lung Foundation, 20180513Swedish Heart Lung Foundation, 20210653The Swedish Brain Foundation, F2022-0216Swedish Research Council, 2017-04949Swedish Research Council, 2022-04263Region Västerbotten
Available from: 2024-02-22 Created: 2024-02-22 Last updated: 2025-02-10Bibliographically approved
Birnefeld, J., Petersson, K., Wåhlin, A., Eklund, A., Birnefeld, E., Qvarlander, S., . . . Zarrinkoob, L. (2024). Cerebral blood flow assessed with phase-contrast magnetic resonance imaging during blood pressure changes with noradrenaline and labetalol: a trial in healthy volunteers . Anesthesiology, 140(4), 669-678
Open this publication in new window or tab >>Cerebral blood flow assessed with phase-contrast magnetic resonance imaging during blood pressure changes with noradrenaline and labetalol: a trial in healthy volunteers 
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2024 (English)In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 140, no 4, p. 669-678Article in journal (Refereed) Published
Abstract [en]

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

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

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

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

Place, publisher, year, edition, pages
Wolters Kluwer, 2024
National Category
Neurology Radiology, Nuclear Medicine and Medical Imaging Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:umu:diva-220047 (URN)10.1097/ALN.0000000000004775 (DOI)37756527 (PubMedID)2-s2.0-85187724522 (Scopus ID)
Funder
Region Västerbotten
Available from: 2024-01-26 Created: 2024-01-26 Last updated: 2024-04-29Bibliographically approved
Zarrinkoob, L., Myrnäs, S., Wåhlin, A., Eklund, A. & Malm, J. (2024). Cerebral blood flow patterns in patients with low-flow carotid artery stenosis, a 4D-PCMRI assessment. Journal of Magnetic Resonance Imaging, 60(4), 1521-1529
Open this publication in new window or tab >>Cerebral blood flow patterns in patients with low-flow carotid artery stenosis, a 4D-PCMRI assessment
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2024 (English)In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 60, no 4, p. 1521-1529Article in journal (Refereed) Published
Abstract [en]

Background: Compromised cerebral blood flow can contribute to future ischemic events in patients with symptomatic carotid artery disease. However, there is limited knowledge of the effects on cerebral hemodynamics resulting from a reduced internal carotid artery (ICA) blood flow rate (BFR).

Purpose: Investigate how reduced ICA-BFR, relates to BFR in the cerebral arteries.

Study Type: Prospective.

Subjects: Thirty-eight patients, age 72 ± 6 years (11 female).

Field Strength/Sequence: 3-Tesla, four-dimensional phase-contrast magnetic resonance imaging (4D-PCMRI).

Assessment: Patients with ischemic stroke or transient ischemic attack were evaluated regarding the degree of stenosis. 4D-PCMRI was used to measure cerebral BFR in 38 patients with symptomatic carotid stenosis (≥50%). BFR in the cerebral arteries was assessed in two subgroups based on symptomatic ICA-BFR: reduced ICA-flow (<160 mL/minutes) and preserved ICA-flow (≥160 mL/minutes). BFR laterality was defined as a difference in the paired ipsilateral-contralateral arteries.

Statistical Tests: Patients were grouped based on ICA-BFR (reduced vs. preserved). Statistical tests (independent sample t-test/paired t-test) were used to compare groups and hemispheres. Significance was determined at P < 0.05.

Results: The degree of stenosis was not significantly different, 80% (95% confidence interval [CI] = 73%–87%) in the reduced ICA-flow vs. 72% (CI = 66%–76%) in the preserved ICA-flow; P = 0.09. In the reduced ICA-flow group, a significantly reduced BFR was found in the ipsilateral middle cerebral artery and anterior cerebral artery (A1), while significantly increased in the contralateral A1. Retrograde BFR was found in the posterior communicating artery and ophthalmic artery. Significant BFR laterality was present in all paired arteries in the reduced ICA-flow group, contrasting the preserved ICA-flow group (P = 0.14–0.93).

Data Conclusions: 4D-PCMRI revealed compromised cerebral BFR due to carotid stenosis, not possible to detect by solely analyzing the degree of stenosis. In patients with reduced ICA-flow, collaterals were not sufficient to maintain symmetrical BFR distribution to the two hemispheres.

Evidence Level: 2.

Technical Efficacy: Stage 3.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
Keywords
4D-PCMRI, cerebral blood flow, cerebrovascular disease, Circle of Willis, MRI, symptomatic carotid stenosis
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-219323 (URN)10.1002/jmri.29216 (DOI)001135005100001 ()38168876 (PubMedID)2-s2.0-85181227868 (Scopus ID)
Funder
Swedish Research Council, 2015-05616Swedish Research Council, 2017-04949Region VästerbottenSwedish Heart Lung Foundation, 20140592
Available from: 2024-01-15 Created: 2024-01-15 Last updated: 2024-12-05Bibliographically approved
Holmgren, M., Henze, A., Wåhlin, A., Eklund, A., Fox, A. J. & Johansson, E. (2024). Diagnostic separation of conventional ⩾50% carotid stenosis and near-occlusion with phase-contrast MRI. European Stroke Journal, 9(1), 135-143
Open this publication in new window or tab >>Diagnostic separation of conventional ⩾50% carotid stenosis and near-occlusion with phase-contrast MRI
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2024 (English)In: European Stroke Journal, ISSN 2396-9873, E-ISSN 2396-9881, Vol. 9, no 1, p. 135-143Article in journal (Refereed) Published
Abstract [en]

Introduction: The aim of this study was to assess sensitivity, specificity and interrater reliability of phase-contrast MRI (PC-MRI) for diagnosing carotid near-occlusion.

Patients and methods: Prospective cross-sectional study conducted between 2018 and 2021. We included participants with suspected 50%–100% carotid stenosis on at least one side, all were examined with CT angiography (CTA) and PC-MRI and both ICAs were analyzed. Degree of stenosis on CTA was the reference test. PC-MRI-based blood flow rates in extracranial ICA and intracranial cerebral arteries were assessed. ICA-cerebral blood flow (CBF) ratio was defined as ICA divided by sum of both ICAs and Basilar artery.

Results: We included 136 participants. The ICAs were 102 < 50% stenosis, 88 conventional ⩾50% stenosis (31 with ⩾70%), 49 near-occlusion, 12 occlusions, 20 unclear cause of small distal ICA on CTA and one excluded. For separation of near-occlusion and conventional stenoses, ICA flow rate and ICA-CBF ratio had the highest area under the curve (AUC; 0.98–0.99) for near-occlusion. ICA-CBF ratio ⩽0.225 was 90% (45/49) sensitive and 99% (188/190) specific for near-occlusion. Inter-rater reliability for this threshold was excellent (kappa 0.98). Specificity was 94% (29/31) for cases with ⩾70% stenosis. PC-MRI had modest performance for separating <50% and conventional ⩾50% stenosis (highest AUC 0.74), and eight (16%) of near-occlusions were not distinguishable from occlusion (no visible flow).

Conclusion: ICA-CBF ratio ⩽0.225 on PC-MRI is an accurate and reliable method to separate conventional ⩾50% stenosis and near-occlusion that is feasible for routine use. PC-MRI should be considered further as a potential standard method for near-occlusion detection, to be used side-by-side with established modalities as PC-MRI cannot separate other degrees of stenosis.

Place, publisher, year, edition, pages
Sage Publications, 2024
Keywords
Carotid stenosis, CT angiography, near-occlusion, phase-contrast MRI
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-217715 (URN)10.1177/23969873231215634 (DOI)001112325800001 ()38032058 (PubMedID)2-s2.0-85178479481 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationRegion VästerbottenSwedish Heart Lung FoundationThe Swedish Stroke AssociationHarald and Greta Jeansson FoundationThe Swedish Medical AssociationUmeå University
Available from: 2023-12-14 Created: 2023-12-14 Last updated: 2024-04-26Bibliographically approved
Pedersen, R., Johansson, J., Nordin, K., Rieckmann, A., Wåhlin, A., Nyberg, L., . . . Salami, A. (2024). Dopamine D1-receptor organization contributes to functional brain architecture. Journal of Neuroscience, 44(11), Article ID e0621232024.
Open this publication in new window or tab >>Dopamine D1-receptor organization contributes to functional brain architecture
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2024 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 44, no 11, article id e0621232024Article in journal (Refereed) Published
Abstract [en]

Recent work has recognized a gradient-like organization in cortical function, spanning from primary sensory to transmodal cortices. It has been suggested that this axis is aligned with regional differences in neurotransmitter expression. Given the abundance of dopamine D1-receptors (D1DR), and its importance for modulation and neural gain, we tested the hypothesis that D1DR organization is aligned with functional architecture, and that inter-regional relationships in D1DR co-expression modulate functional cross talk. Using the world's largest dopamine D1DR-PET and MRI database (N = 180%, 50% female), we demonstrate that D1DR organization follows a unimodal–transmodal hierarchy, expressing a high spatial correspondence to the principal gradient of functional connectivity. We also demonstrate that individual differences in D1DR density between unimodal and transmodal regions are associated with functional differentiation of the apices in the cortical hierarchy. Finally, we show that spatial co-expression of D1DR primarily modulates couplings within, but not between, functional networks. Together, our results show that D1DR co-expression provides a biomolecular layer to the functional organization of the brain.

Place, publisher, year, edition, pages
Society for Neuroscience, 2024
Keywords
architecture, dopamine, functional connectivity, gradients, organization
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-222641 (URN)10.1523/JNEUROSCI.0621-23.2024 (DOI)38302439 (PubMedID)2-s2.0-85187783583 (Scopus ID)
Available from: 2024-04-19 Created: 2024-04-19 Last updated: 2024-07-02Bibliographically approved
Vikström, A., Holmlund, P., Holmgren, M., Wåhlin, A., Zarrinkoob, L., Malm, J. & Eklund, A. (2024). Establishing the distribution of cerebrovascular resistance using computational fluid dynamics and 4D flow MRI. Scientific Reports, 14(1), Article ID 14585.
Open this publication in new window or tab >>Establishing the distribution of cerebrovascular resistance using computational fluid dynamics and 4D flow MRI
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2024 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, no 1, article id 14585Article in journal (Refereed) Published
Abstract [en]

Cerebrovascular resistance (CVR) regulates blood flow in the brain, but little is known about the vascular resistances of the individual cerebral territories. We present a method to calculate these resistances and investigate how CVR varies in the hemodynamically disturbed brain. We included 48 patients with stroke/TIA (29 with symptomatic carotid stenosis). By combining flow rate (4D flow MRI) and structural computed tomography angiography (CTA) data with computational fluid dynamics (CFD) we computed the perfusion pressures out from the circle of Willis, with which CVR of the MCA, ACA, and PCA territories was estimated. 56 controls were included for comparison of total CVR (tCVR). CVR were 33.8 ± 10.5, 59.0 ± 30.6, and 77.8 ± 21.3 mmHg s/ml for the MCA, ACA, and PCA territories. We found no differences in tCVR between patients, 9.3 ± 1.9 mmHg s/ml, and controls, 9.3 ± 2.0 mmHg s/ml (p = 0.88), nor in territorial CVR in the carotid stenosis patients between ipsilateral and contralateral hemispheres. Territorial resistance associated inversely to territorial brain volume (p < 0.001). These resistances may work as reference values when modelling blood flow in the circle of Willis, and the method can be used when there is need for subject-specific analysis.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Neurosciences Physiology and Anatomy Medical Imaging Computational Mathematics
Identifiers
urn:nbn:se:umu:diva-227152 (URN)10.1038/s41598-024-65431-4 (DOI)2-s2.0-85196758949 (Scopus ID)
Funder
Swedish Research Council, 2015-05616Swedish Research Council, 2017-04949Region VästerbottenSwedish Heart Lung FoundationSwedish Foundation for Strategic Research
Available from: 2024-06-25 Created: 2024-06-25 Last updated: 2025-02-10Bibliographically approved
van Osch, M. J. P., Wåhlin, A., Scheyhing, P., Mossige, I., Hirschler, L., Eklund, A., . . . Ringstad, G. (2024). Human brain clearance imaging: pathways taken by magnetic resonance imaging contrast agents after administration in cerebrospinal fluid and blood. NMR in Biomedicine, 37(9), Article ID e5159.
Open this publication in new window or tab >>Human brain clearance imaging: pathways taken by magnetic resonance imaging contrast agents after administration in cerebrospinal fluid and blood
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2024 (English)In: NMR in Biomedicine, ISSN 0952-3480, E-ISSN 1099-1492, Vol. 37, no 9, article id e5159Article, review/survey (Refereed) Published
Abstract [en]

Over the last decade, it has become evident that cerebrospinal fluid (CSF) plays a pivotal role in brain solute clearance through perivascular pathways and interactions between the brain and meningeal lymphatic vessels. Whereas most of this fundamental knowledge was gained from rodent models, human brain clearance imaging has provided important insights into the human system and highlighted the existence of important interspecies differences. Current gold standard techniques for human brain clearance imaging involve the injection of gadolinium-based contrast agents and monitoring their distribution and clearance over a period from a few hours up to 2 days. With both intrathecal and intravenous injections being used, which each have their own specific routes of distribution and thus clearance of contrast agent, a clear understanding of the kinetics associated with both approaches, and especially the differences between them, is needed to properly interpret the results. Because it is known that intrathecally injected contrast agent reaches the blood, albeit in small concentrations, and that similarly some of the intravenously injected agent can be detected in CSF, both pathways are connected and will, in theory, reach the same compartments. However, because of clear differences in relative enhancement patterns, both injection approaches will result in varying sensitivities for assessment of different subparts of the brain clearance system. In this opinion review article, the "EU Joint Programme – Neurodegenerative Disease Research (JPND)" consortium on human brain clearance imaging provides an overview of contrast agent pharmacokinetics in vivo following intrathecal and intravenous injections and what typical concentrations and concentration–time curves should be expected. This can be the basis for optimizing and interpreting contrast-enhanced MRI for brain clearance imaging. Furthermore, this can shed light on how molecules may exchange between blood, brain, and CSF.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
Keywords
brain clearance, cerebrospinal fluid, glymphatics, intrathecal injection, intravenous injection
National Category
Radiology, Nuclear Medicine and Medical Imaging Neurosciences
Identifiers
urn:nbn:se:umu:diva-224080 (URN)10.1002/nbm.5159 (DOI)001204639900001 ()38634301 (PubMedID)2-s2.0-85190949684 (Scopus ID)
Funder
EU, Horizon 2020, 825664Swedish Research Council, 2022-04263Swedish Foundation for Strategic ResearchThe Research Council of Norway, 333956
Available from: 2024-05-13 Created: 2024-05-13 Last updated: 2024-08-20Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0001-6784-1945

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