| 1. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 2. |
- Björnfot, Cecilia, et al.
(författare)
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Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults : a 4D flow MRI study
- 2024
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016.
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Vikner, Tomas, et al.
(författare)
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5-year associations among cerebral arterial pulsatility, perivascular space dilation, and white matter lesions
- 2022
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 92:5, s. 871-881
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Vikner, Tomas, et al.
(författare)
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Blood-brain barrier integrity is linked to cognitive function, but not to cerebral arterial pulsatility, among elderly
- 2024
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
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| 6. |
- Allentoft, Morten E., et al.
(författare)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 7. |
- Ambarki, Khalid, et al.
(författare)
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Accuracy of Parenchymal Cerebral Blood Flow Measurements Using Pseudocontinuous Arterial Spin-labeling in Healthy Volunteers
- 2015
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Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 36:10, s. 1816-1821
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The arterial spin-labeling method for CBF assessment is widely available, but its accuracy is not fully established. We investigated the accuracy of a whole-brain arterial spin-labeling technique for assessing the mean parenchymal CBF and the effect of aging in healthy volunteers. Phase-contrast MR imaging was used as the reference method. MATERIALS AND METHODS: Ninety-two healthy volunteers were included: 49 young (age range, 20-30 years) and 43 elderly (age range, 65-80 years). Arterial spin-labeling parenchymal CBF values were averaged over the whole brain to quantify the mean pCBF(ASL) value. Total. CBF was assessed with phase-contrast MR imaging as the sum of flows in the internal carotid and vertebral arteries, and subsequent division by brain volume returned the pCBF(PCMRI) value. Accuracy was considered as good as that of the reference method if the systematic difference was less than 5 mL/min/100 g of brain tissue and if the 95% confidence intervals were equal to or better than +/- 10 mL/min/100 g. RESULTS: pCBF(ASL) correlated to pCBF(PCMRI) (r = 0.73; P < .001). Significant differences were observed between the pCBF(ASL) and pCBF(PCMRI) values in the young (P = .001) and the elderly (P < .001) volunteers. The systematic differences (mean 2 standard deviations) were -4 +/- 14 mL/min/100 g in the young subjects and 6 +/- 12 mL/min/100 g in the elderly subjects. Young subjects showed higher values than the elderly subjects for pCBF(PCMRI) (young, 57 +/- 8 mL/min/100 g; elderly, 54 +/- 7 mL/min/100 g; P = .05) and pCBF(ASL) (young, 61 +/- 10 mL/min/100 g; elderly, 48 +/- 10 mL/min/100 g; P < .001). CONCLUSIONS: The limits of agreement were too wide for the arterial spin-labeling method to be considered satisfactorily accurate, whereas the systematic overestimation in the young subjects and underestimation in the elderly subjects were close to acceptable. The age-related decrease in parenchymal CBF was augmented in arterial spin-labeling compared with phase-contrast MR imaging.
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| 8. |
- Ambarki, Khalid, et al.
(författare)
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Blood flow of ophthalmic artery in healthy individuals determined by phase-contrast magnetic resonance imaging
- 2013
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 54:4, s. 2738-2745
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Ambarki, Khalid, et al.
(författare)
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Brain ventricular size in healthy elderly: comparison between evans index and volume measurement.
- 2010
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Ingår i: Neurosurgery. - : Lippincott Williams & Wilkins. - 0148-396X .- 1524-4040. ; 67:1, s. 94-99
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Ambarki, Khalid, et al.
(författare)
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Evaluation of Automatic Measurement of the Intracranial Volume Based on Quantitative MR Imaging
- 2012
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Ingår i: American Journal of Neuroradiology. - : American Society of Neuroradiology. - 0195-6108 .- 1936-959X. ; 33:10, s. 1951-1956
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Tidskriftsartikel (refereegranskat)abstract
- 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 greater than .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 less than1%. 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.
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| 11. |
- Ambarki, Khalid, et al.
(författare)
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MR imaging of brain volumes : evaluation of a fully automatic software
- 2011
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Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 32:2, s. 408-412
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 12. |
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| 13. |
- Birnefeld, Johan, et al.
(författare)
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Cerebral arterial pulsatility is associated with features of small vessel disease in patients with acute stroke and TIA : a 4D flow MRI study
- 2020
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Ingår i: Journal of Neurology. - : Springer. - 0340-5354 .- 1432-1459. ; 267:3, s. 721-730
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral small vessel disease (SVD) is a major cause of stroke and cognitive impairment. However, the underlying mechanisms behind SVD are still poorly understood. High cerebral arterial pulsatility has been suggested as a possible cause of SVD. In population studies, arterial pulsatility has been linked to white matter hyperintensities (WMH), cerebral atrophy, and cognitive impairment, all features of SVD. In stroke, pulsatility data are scarce and contradictory. The aim of this study was to investigate the relationship between arterial pulsatility and SVD in stroke patients. With a cross-sectional design, 89 patients with acute ischemic stroke or TIA were examined with MRI. A neuropsychological assessment was performed 1 year later. Using 4D flow MRI, pulsatile indices (PI) were calculated for the internal carotid artery (ICA) and middle cerebral artery (M1, M3). Flow volume pulsatility (FVP), a measure corresponding to the cyclic expansion of the arterial tree, was calculated for the same locations. These parameters were assessed for associations with WMH volume, brain volume and cognitive function. ICA-FVP was associated with WMH volume (β = 1.67, 95% CI: [0.1, 3.24], p = 0.037). M1-PI and M1-FVP were associated with decreasing cognitive function (β = - 4.4, 95% CI: [- 7.7, - 1.1], p = 0.009 and β = - 13.15, 95% CI: [- 24.26, - 2.04], p = 0.02 respectively). In summary, this supports an association between arterial pulsatility and SVD in stroke patients, and provides a potential target for further research and preventative treatment. FVP may become a useful biomarker for assessing pulsatile stress with PCMRI and 4D flow MRI.
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| 14. |
- Birnefeld, Johan, et al.
(författare)
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Cerebral blood flow assessed with phase-contrast magnetic resonance imaging during blood pressure changes with noradrenaline and labetalol : a trial in healthy volunteers
- 2024
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Ingår i: Anesthesiology. - : Wolters Kluwer. - 0003-3022 .- 1528-1175. ; 140:4, s. 669-678
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adequate cerebral perfusion is central during general anesthesia. However, perfusion is not readily measured bedside. Clinicians currently rely mainly on MAP as a surrogate even though the relationship between blood pressure and cerebral blood flow is not well understood. The aim of this study was to apply phase contrast MRI to characterize blood flow responses in healthy volunteers to commonly used pharmacological agents that increase or decrease arterial blood pressure.Methods: Eighteen healthy volunteers aged 30-50 years were investigated with phase contrast MRI. Intraarterial blood pressure monitoring was used. First, intravenous noradrenaline was administered to a target MAP of 20% above baseline. After a wash-out period, intravenous labetalol was given to a target MAP of 15% below baseline. Cerebral blood flow was measured using phase contrast MRI and defined as the sum of flow in the internal carotid arteries and vertebral arteries. CO was defined as the flow in the ascending aorta.Baseline median cerebral blood flow was 772 ml/min (interquartile range, 674 to 871), and CO was 5,874 ml/min (5,199 to 6,355). The median dose of noradrenaline was 0.17 µg · kg−1 · h−1 (0.14 to 0.22). During noradrenaline infusion, cerebral blood flow decreased to 705 ml/min (606 to 748; P = 0.001), and CO decreased to 4,995 ml/min (4,705 to 5,635; P = 0.01). A median dose of labetalol was 120 mg (118 to 150). After labetalol boluses, cerebral blood flow was unchanged at 769 ml/min (734 to 900; P = 0.68). CO increased to 6,413 ml/min (6,056 to 7,464; P = 0.03).Conclusion: In healthy awake subjects, increasing MAP using intravenous noradrenaline decreased cerebral blood flow and CO. This data does not support inducing hypertension with noradrenaline to increase cerebral blood flow. Cerebral blood flow was unchanged when decreasing MAP using labetalol.
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| 15. |
- Birnefeld, Johan, 1989-
(författare)
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Cerebral hemodynamics in stroke, cerebral small vessel disease and pharmacological interventions : a 4D flow MRI study
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aim: Current cerebrovascular imaging techniques provide important information on arterial anatomy and structural pathologies, such as stenoses and occlusions, but physicians are left to infer how the blood flow is affected. In addition, the relationship between blood pressure and cerebral blood flow is complex and poorly understood. Increased transmission of cardiac pulsatility to the cerebral microvasculature has been suggested as a causative factor of cerebral small vessel disease (CSVD) but previous research have yielded conflicting results regarding this relationship. 4D flow magnetic resonance imaging (MRI) is a novel and promising technique enabling time-resolved blood flow quantification with whole-brain coverage and relatively short scan times. However, despite its obvious potential, there is not yet an evidence-based application for the use of 4D flow MRI within stroke or CSVD. This dissertation aimed to apply 4D flow MRI to describe blood flow patterns in posterior circulation stroke and cerebral blood flow responses to common pharmacological agents used to alter arterial blood pressure as well as to examine the relationship between cerebral arterial pulsatility and CSVD.Methods and Results: This doctoral dissertation consisted of four papers, referred to by roman numerals. 4D flow MRI and computed tomography angiography (CTA) were applied in 25 patients with acute ischemic stroke in the posterior circulation and a reference population of 15 healthy elderly (paper I). Individual flow profiles were created for each stroke patient and hemodynamic disturbances as well as collateral compensation were described. We show that hemodynamic findings were related to structural findings from CTA.The cross-sectional relationship between cerebral arterial pulsatility (quantified using 4D flow MRI as pulsatility index [PI] and flow volume pulsatility [FVP]) and features of CSVD were examined using regression analysis in 89 patients with acute ischemic stroke (paper II) and a population-based sample of 862 elderly (paper III). Internal carotid artery FVP was associated with increasing white matter hyperintensity (WMH) volume in patients with stroke and TIA (paper II). In addition, increasing middle cerebral artery FVP and PI were associated with worse cognitive function. In the population sample, high FVP and PI were associated with increasing WMH volume, lower brain volume and the presence of lacunes, but not the composite MRI-CSVD (paper III). Among subjects with MRI-CSVD, displaying symptoms consistent with cerebral small vessel disease was associated with higher WMH volume, lower brain volume and active smoking, but not any measure of pulsatility.Eighteen healthy volunteers were administered noradrenaline to increase mean arterial pressure by 20% above baseline, and labetalol to decrease mean arterial pressure to 15% below baseline (paper IV). Cerebral blood flow was measured using phase-contrast MRI at each blood pressure level and compared to baseline. Despite a marked increase in blood pressure, noradrenaline administration caused a reduction in cerebral blood flow and cardiac output. Meanwhile, labetalol administration caused no change in cerebral blood flow but an increased cardiac output.Conclusions: 4D flow MRI can detect hemodynamic disturbances and discriminate between hemodynamic disturbances and normal flow in patients with structural vascular pathologies. This additional information compared to structural imaging alone could potentially be used for prognosis and selection for procedures in clinical care. Cerebral arterial pulsatility is modestly associated with several MRI and clinical features of CSVD but not all. Cerebral arterial pulsatility as the main risk factor of CSVD seems unlikely but its involvement in the pathophysiology cannot be ruled out. Raising the blood pressure with noradrenaline decreases cerebral blood flow and cardiac output without any redistribution from peripheral to cerebral flow. This highlights the pitfalls of using blood pressure as a surrogate for cerebral blood flow and questions the validity of our understanding of cerebral autoregulation. Lowering the blood pressure with labetalol does not affect cerebral blood flow, reassuring its use in clinical routine. 4D flow MRI can be integrated into an in-patient work-up in selected cases of acute ischemic stroke and into the workflow of large epidemiological studies.
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| 16. |
- Dunås, Tora, et al.
(författare)
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4D flow MRI : automatic assessment of blood flow in cerebral arteries
- 2019
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Ingår i: Biomedical Engineering & Physics Express. - : Institute of Physics Publishing (IOPP). - 2057-1976. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: With a 10-minute 4D flow MRI scan, the distribution of blood flow to individual arteries throughout the brain can be analyzed. This technique has potential to become a biomarker for treatment decisions, and to predict prognosis after stroke. To efficiently analyze and model the large dataset in clinical practice, automatization is needed. We hypothesized that identification of selected arterial regions using an atlas with a priori probability information on their spatial distribution can provide standardized measurements of blood flow in the main cerebral arteries.Approach: A new method for automatic placement of measurement locations in 4D flow MRI was developed based on an existing atlas-based method for arterial labeling, by defining specific regions of interest within the corresponding arterial atlas. The suggested method was evaluated on 38 subjects with carotid artery stenosis, by comparing measurements of blood flow rate at automatically selected locations to reference measurements at manually selected locations.Main results: Automatic and reference measurement ranged from 10 to 580 ml min−1 and were highly correlated (r = 0.99) with a mean flow difference of 0.61 ± 10.7 ml min−1 (p = 0.21). Out of the 559 arterial segments in the manual reference, 489 were correctly labeled, yielding a sensitivity of 88%, a specificity of 85%, and a labeling accuracy of 87%.Significance: This study confirms that atlas-based labeling of 4D flow MRI data is suitable for efficient flow quantification in the major cerebral arteries. The suggested method improves the feasibility of analyzing cerebral 4D flow data, and fills a gap necessary for implementation in clinical use.
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| 17. |
- Dunås, Tora, et al.
(författare)
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A Stereotactic Probabilistic Atlas for the Major Cerebral Arteries
- 2017
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Ingår i: Neuroinformatics. - : Springer Science and Business Media LLC. - 1539-2791 .- 1559-0089. ; 15:1, s. 101-110
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Tidskriftsartikel (refereegranskat)abstract
- Improved whole brain angiographic and velocity-sensitive MRI is pushing the boundaries of noninvasively obtained cerebral vascular flow information. The complexity of the information contained in such datasets calls for automated algorithms and pipelines, thus reducing the need of manual analyses by trained radiologists. The objective of this work was to lay the foundation for such automated pipelining by constructing and evaluating a probabilistic atlas describing the shape and location of the major cerebral arteries. Specifically, we investigated how the implementation of a non-linear normalization into Montreal Neurological Institute (MNI) space improved the alignment of individual arterial branches. In a population-based cohort of 167 subjects, age 64-68 years, we performed 4D flow MRI with whole brain volumetric coverage, yielding both angiographic and anatomical data. For each subject, sixteen cerebral arteries were manually labeled to construct the atlas. Angiographic data were normalized to MNI space using both rigid-body and non-linear transformations obtained from anatomical images. The alignment of arterial branches was significantly improved by the non-linear normalization (p < 0.001). Validation of the atlas was based on its applicability in automatic arterial labeling. A leave-one-out validation scheme revealed a labeling accuracy of 96 %. Arterial labeling was also performed in a separate clinical sample (n = 10) with an accuracy of 92.5 %. In conclusion, using non-linear spatial normalization we constructed an artery-specific probabilistic atlas, useful for cerebral arterial labeling.
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| 18. |
- Dunås, Tora, et al.
(författare)
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Accuracy of blood flow assessment in cerebral arteries with 4D flow MRI : Evaluation with three segmentation methods
- 2019
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586. ; 50:2, s. 511-518
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accelerated 4D flow MRI allows for high‐resolution velocity measurements with whole‐brain coverage. Such scans are increasingly used to calculate flow rates of individual arteries in the vascular tree, but detailed information about the accuracy and precision in relation to different postprocessing options is lacking.Purpose: To evaluate and optimize three proposed segmentation methods and determine the accuracy of in vivo 4D flow MRI blood flow rate assessments in major cerebral arteries, with high‐resolution 2D PCMRI as a reference.Study Type: Prospective.Subjects: Thirty‐five subjects (20 women, 79 ± 5 years, range 70–91 years).Field Strength/Sequence: 4D flow MRI with PC‐VIPR and 2D PCMRI acquired with a 3 T scanner.Assessment: We compared blood flow rates measured with 4D flow MRI, to the reference, in nine main cerebral arteries. Lumen segmentation in the 4D flow MRI was performed with k‐means clustering using four different input datasets, and with two types of thresholding methods. The threshold was defined as a percentage of the maximum intensity value in the complex difference image. Local and global thresholding approaches were used, with evaluated thresholds from 6–26%.Statistical Tests: Paired t‐test, F‐test, linear correlation (P < 0.05 was considered significant) along with intraclass correlation (ICC).Results: With the thresholding methods, the lowest average flow difference was obtained for 20% local (0.02 ± 15.0 ml/min, ICC = 0.97, n = 310) or 10% global (0.08 ± 17.3 ml/min, ICC = 0.97, n = 310) thresholding with a significant lower standard deviation for local (F‐test, P = 0.01). For all clustering methods, we found a large systematic underestimation of flow compared with 2D PCMRI (16.1–22.3 ml/min).Data Conclusion: A locally adapted threshold value gives a more stable result compared with a globally fixed threshold. 4D flow with the proposed segmentation method has the potential to become a useful reliable clinical tool for assessment of blood flow in the major cerebral arteries.Level of Evidence: 2Technical Efficacy: Stage 2
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| 19. |
- Dunås, Tora, et al.
(författare)
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Automatic labeling of cerebral arteries in magnetic resonance angiography
- 2016
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Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661. ; 29:1, s. 39-47
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 20. |
- Dunås, Tora, 1988-
(författare)
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Blood flow assessment in cerebral arteries with 4D flow magnetic resonance imaging : an automatic atlas-based approach
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Disturbed blood flow to the brain has been associated with several neurological diseases, from stroke and vascular diseases to Alzheimer’s and cognitive decline. To determine the cerebral arterial blood flow distribution, measurements are needed in both distal and proximal arteries.4D flow MRI makes it possible to obtain blood flow velocities from a volume covering the entire brain in one single scan. This facilitates more extensive flow investigations, since flow rate assessment in specific arteries can be done during post-processing. The flow rate assessment is still rather laborious and time consuming, especially if the number of arteries of interest is high. In addition, the quality of the measurements relies heavily on the expertise of the investigator.The aim of this thesis was to develop and evaluate an automatic post-processing tool for 4D flow MRI that identifies the main cerebral arteries and calculates their blood flow rate with minimal manual input. Atlas-based labeling of brain tissue is common in toolboxes for analysis of neuroimaging-data, and we hypothesized that a similar approach would be suitable for arterial labeling. We also wanted to investigate how to best separate the arterial lumen from background for calculation of blood flow.Methods: An automatic atlas-based arterial identification method (AAIM) for flow assessment was developed. With atlas-based labeling, voxels are labeled based on their spatial location in MNI-space, a stereotactic coordinate system commonly used for neuroimaging analysis. To evaluate the feasibility of this approach, a probabilistic atlas was created from a set of angiographic images derived from 4D flow MRI. Included arteries were the anterior (ACA), middle (MCA) and posterior (PCA) cerebral arteries, as well as the internal carotid (ICA), vertebral (VA), basilar (BA) and posterior communicating (PCoA) arteries. To identify the arteries in an angiographic image, a vascular skeleton where each branch represented an arterial segment was extracted and labeled according to the atlas. Labeling accuracy of the AAIM was evaluated by visual inspection.Next, the labeling method was adapted for flow measurements by pre-defining desired regions within the atlas. Automatic flow measurements were then compared to measurements at manually identified locations. During the development process, arterial identification was evaluated on four patient cohorts, with and without vascular disease. Finally, three methods for flow quantification using 4D flow MRI: k-means clustering; global thresholding; and local thresholding, were evaluated against a standard reference method.Results: The labeling accuracy on group level was between 96% and 87% for all studies, and close to 100% for ICA and BA. Short arteries (PCoA) and arteries with large individual anatomical variation (VA) were the most challenging. Blood flow measurements at automatically identified locations were highly correlated (r=0.99) with manually positioned measurements, and difference in mean flow was negligible.Both global and local thresholding out-performed k-means clustering, since the threshold value could be optimized to produce a mean difference of zero compared to reference. The local thresholding had the best concordance with the reference method (p=0.009, F-test) and was the only method that did not have a significant correlation between flow difference and flow rate. In summary, with a local threshold of 20%, ICC was 0.97 and the flow rate difference was -0.04 ± 15.1 ml/min, n=308.Conclusion: This thesis work demonstrated that atlas-based labeling was suitable for identification of cerebral arteries, enabling automated processing and flow assessment in 4D flow MRI. Furthermore, the proposed flow rate quantification algorithm reduced some of the most important shortcomings associated with previous methods. This new platform for automatic 4D flow MRI data analysis fills a gap needed for efficient in vivo investigations of arterial blood flow distribution to the entire vascular tree of the brain, and should have important applications to practical use in neurological diseases.
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| 21. |
- Dunås, Tora, et al.
(författare)
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Towards Automatic Identification of Cerebral Arteries in 4D Flow MRI
- 2015
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Ingår i: 16th Nordic-Baltic Conference on Biomedical Engineering. - Cham : Springer International Publishing. - 9783319129662 - 9783319129679 ; , s. 40-43
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Konferensbidrag (refereegranskat)abstract
- 4D flow MRI is a powerful imaging technique which provides an angiographic image with information about blood flow in a large volume, time resolved over the cardiac cycle, in a short imaging time. This study aims to develop an automatic method for identification of cerebral arteries. The proposed method is based on an atlas of twelve arteries, developed from 4D flow MRI of 25 subjects. The atlas was constructed by normalizing all images to MNI-space, manually identifying the arteries and creating an average over the volume. The identification is done by extracting a vascular skeleton from the image, transforming it to MNI-space, labeling it with the atlas and transforming it back to subject space. The method was evaluated on a pilot cohort of 8 subjects. The rate of correctly identified arteries was 97%.
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| 22. |
- Eklund, Anders, et al.
(författare)
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The Pressure Difference between Eye and Brain Changes with Posture
- 2016
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 80:2, s. 269-276
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The discovery of a posture-dependent effect on the difference between intraocular pressure (IOP) and intracranial pressure (ICP) at the level of lamina cribrosa could have important implications for understanding glaucoma and idiopathic intracranial hypertension and could help explain visual impairments in astronauts exposed to microgravity. The aim of this study was to determine the postural influence on the difference between simultaneously measured ICP and IOP.Methods: Eleven healthy adult volunteers (age = 46 ± 10 years) were investigated with simultaneous ICP, assessed through lumbar puncture, and IOP measurements when supine, sitting, and in 9° head-down tilt (HDT). The trans–lamina cribrosa pressure difference (TLCPD) was calculated as the difference between the IOP and ICP. To estimate the pressures at the lamina cribrosa, geometrical distances were estimated from magnetic resonance imaging and used to adjust for hydrostatic effects.Results: The TLCPD (in millimeters of mercury) between IOP and ICP was 12.3 ± 2.2 for supine, 19.8 ± 4.6 for sitting, and 6.6 ± 2.5 for HDT. The expected 24-hour average TLCPD on earth—assuming 8 hours supine and 16 hours upright—was estimated to be 17.3mmHg. By removing the hydrostatic effects on pressure, a corresponding 24-hour average TLCPD in microgravity environment was simulated to be 6.7mmHg.Interpretation: We provide a possible physiological explanation for how microgravity can cause symptoms similar to those seen in patients with elevated ICP. The observed posture dependency of TLCPD also implies that assessment of the difference between IOP and ICP in upright position may offer new understanding of the pathophysiology of idiopathic intracranial hypertension and glaucoma.
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| 23. |
- Ekman, Urban, et al.
(författare)
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Increase of frontal neuronal activity in chronic neglect after training in virtual reality
- 2018
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Ingår i: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 138:4, s. 284-292
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: A third of patients with stroke acquire spatial neglect associated with poor rehabilitation outcome. New effective rehabilitation interventions are needed. Scanning training combined with multisensory stimulation to enhance the rehabilitation effect is suggested. In accordance, we have designed a virtual-reality based scanning training that combines visual, audio and sensori-motor stimulation called RehAtt((R)). Effects were shown in behavioural tests and activity of daily living. Here, we use fMRI to evaluate the change in brain activity during Posners Cuing Task (attention task) after RehAtt((R)) intervention, in patients with chronic neglect.Methods: Twelve patients (mean age=72.7years, SD=6.1) with chronic neglect (persistent symptoms >6months) performed the interventions 3 times/wk during 5weeks, in total 15hours. Training effects on brain activity were evaluated using fMRI task-evoked responses during the Posners cuing task before and after the intervention.Results: Patients improved their performance in the Posner fMRI task. In addition, patients increased their task-evoked brain activity after the VR interventions in an extended network including pre-frontal and temporal cortex during attentional cueing, but showed no training effects during target presentations.Conclusions: The current pilot study demonstrates that a novel multisensory VR intervention has the potential to benefit patients with chronic neglect in respect of behaviour and brain changes. Specifically, the fMRI results show that strategic processes (top-down control during attentional cuing) were enhanced by the intervention. The findings increase knowledge of the plasticity processes underlying positive rehabilitation effects from RehAtt((R)) in chronic neglect.
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| 24. |
- Holmgren, Madelene, 1992-
(författare)
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4D flow MRI and modelling to assess cerebral arterial hemodynamics : method development and evaluation, with implementation in patients with symptomatic carotid stenosis
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Blood flow measurements are important for understanding the development of cerebrovascular diseases. With 4D flow magnetic resonance imaging (4D flow MRI), simultaneous velocity measurements are obtained in all cerebral arteries in a scan of about ten minutes. However, 4D flow MRI is a relatively new technique. For usefulness in both clinics and research, detailed knowledge is needed about its accuracy and precision for flow quantification. In patients with stroke or transient ischemic attack (TIA) from a symptomatic carotid stenosis, the stenosis may generate a difference in blood pressure and flow between the left and right cerebral hemispheres. Such a hemispheric pressure difference could be an early marker of to what extent a stenosis is affecting cerebral hemodynamics, which could be useful in the planning of carotid surgery. The overall aim of the thesis was to determine the accuracy of 4D flow MRI to measure cerebral arterial blood flow, and to develop and evaluate an approach combining 4D flow MRI and computational fluid dynamics (CFD) to characterize the cerebral arterial hemodynamics, with implementation in patients with symptomatic carotid stenosis. The thesis is based on four papers, investigating two cohorts.The first cohort consisted of 35 elderly volunteers (mean age 79 years) and was studied in paper I-II. Blood flow rates were measured in nine cerebral arteries with 4D flow MRI and 2D phase-contrast MRI as reference. Three different flow quantification methods for 4D flow MRI were evaluated and optimized: one clustering approach and two threshold-based methods. The proposed new method, based on a locally adapted threshold, outperformed the previously suggested methods in flow rate quantification. For the clustering method, flow rates were systematically underestimated. 4D flow MRI was also evaluated to assess different arterial pulsatility measures, and a Windkessel model was used to estimate reference values for cerebrovascular resistance and cerebral arterial compliance in elderly.The second cohort consisted of 28 stroke and TIA patients (mean age 73 years) with symptomatic carotid stenosis and was studied in paper III-IV. With 4D flow MRI and CFD, the preoperative hemispheric pressure laterality was quantified in the patients. The pressure laterality was compared to hemispheric flow lateralities. Estimating the hemispheric pressure laterality was a promising physiological biomarker for grading the cerebral arterial hemodynamic disturbances in patients with symptomatic carotid stenosis. A CFD model was also developed to predict carotid stump pressure, i.e., the important pressure measured in the clamped carotid artery during surgical removal of the stenosis. The predicted stump pressures were correlated with the pressures measured during surgery. Stump pressure prediction was promising and could be a potential tool in the preoperative planning in order to avoid hypoperfusion during surgery. In summary, post-processing methods were successfully developed and evaluated for accurate assessment of mean and pulsatile cerebral blood flow rates with 4D flow MRI. Thereby, this thesis provided knowledge about possibilities and limitations of how 4D flow MRI can be used with respect to cerebral arterial blood flow rate assessment. By contributing with models combining 4D flow MRI and CFD, specifically developed for analysis of pressure distributions in cerebral arteries, novel methods were proposed for assessing patients with symptomatic carotid stenosis in the planning of carotid surgery.
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| 25. |
- Holmgren, Madelene, et al.
(författare)
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Assessment of Cerebral Blood Flow Pulsatility and Cerebral Arterial Compliance With 4D Flow MRI
- 2020
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley-Blackwell. - 1053-1807 .- 1522-2586. ; 51:5, s. 1516-1525
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Four-dimensional flow magnetic resonance imaging (4D flow MRI) enables efficient investigation of cerebral blood flow pulsatility in the cerebral arteries. This is important for exploring hemodynamic mechanisms behind vascular diseases associated with arterial pulsations.PURPOSE: To investigate the feasibility of pulsatility assessments with 4D flow MRI, its agreement with reference two-dimensional phase-contrast MRI (2D PC-MRI) measurements, and to demonstrate how 4D flow MRI can be used to assess cerebral arterial compliance and cerebrovascular resistance in major cerebral arteries.STUDY TYPE: Prospective.SUBJECTS: Thirty-five subjects (20 women, 79 ± 5 years, range 70-91 years).FIELD STRENGTH/SEQUENCE: 4D flow MRI (PC-VIPR) and 2D PC-MRI acquired with a 3T scanner.ASSESSMENT: Time-resolved flow was assessed in nine cerebral arteries. From the pulsatile flow waveform in each artery, amplitude (ΔQ), volume load (ΔV), and pulsatility index (PI) were calculated. To reduce high-frequency noise in the 4D flow MRI data, the flow waveforms were low-pass filtered. From the total cerebral blood flow, total PI (PItot ), total volume load (ΔVtot ), cerebral arterial compliance (C), and cerebrovascular resistance (R) were calculated.STATISTICAL TESTS: Two-tailed paired t-test, intraclass correlation (ICC).RESULTS: There was no difference in ΔQ between 4D flow MRI and the reference (0.00 ± 0.022 ml/s, mean ± SEM, P = 0.97, ICC = 0.95, n = 310) with a cutoff frequency of 1.9 Hz and 15 cut plane long arterial segments. For ΔV, the difference was -0.006 ± 0.003 ml (mean ± SEM, P = 0.07, ICC = 0.93, n = 310) without filtering. Total R was 11.4 ± 2.41 mmHg/(ml/s) (mean ± SD) and C was 0.021 ± 0.009 ml/mmHg (mean ± SD). ΔVtot was 1.21 ± 0.29 ml (mean ± SD) with an ICC of 0.82 compared with the reference. PItot was 1.08 ± 0.21 (mean ± SD).DATA CONCLUSION: We successfully assessed 4D flow MRI cerebral arterial pulsatility, cerebral arterial compliance, and cerebrovascular resistance. Averaging of multiple cut planes and low-pass filtering was necessary to assess accurate peak-to-peak features in the flow rate waveforms.LEVEL OF EVIDENCE: 2Technical Efficacy Stage: 2
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