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- 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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- 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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- 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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- Kristiansen, Martin, et al.
(författare)
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Blood flow rate of ophthalmic artery in patients with normal tension glaucoma and healthy controls
- 2018
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Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 59:9
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: To determine the blood flow rate of the ophthalmic artery (OA) in patients with Normal Tension Glaucoma (NTG) compared to age-matched healthy controls using phase-contrast magnetic resonance imaging (PCMRI).Methods: Seventeen patients with treated NTG (11 female; mean age: 70±9 years) and 16 age-matched healthy controls (10 female; mean age: 71±9 years) underwent PCMRI using a 3-Tesla scanner as well as ophthalmological examinations including visual acuity, Goldmann Applanation Tonometry, Humphrey perimetry and fundoscopy. Ophthalmic blood flow was acquired using a 2D PCMRI sequence set to a spatial resolution of 0.35mm/pixel. Mean flow rate and cross-sectional area was calculated using Segment Software. The eye with the most severe glaucomatous damage classified by visual field index (VFI) was chosen for comparison. The primary outcome was blood flow rate of OA.Results: The mean VFI was 41% ± 26 (mean±SD) for the worse NTG eyes. The intraocular pressure was 13.6±2.6 mmHg for NTG eyes and 13.8±2.1 mmHg for control eyes. The blood flow rate in the NTG group was 9.6±3.7 ml/min compared to 11.8±5.5 ml/min in the control group. The area was 1.7±0.3 mm2 and 2.0±0.6 mm2 respectively. No statistical significance was found between NTG and the control group regarding blood flow rate (p=0.07) or OA area (p=0.12).Conclusions: Despite OA being an anastomosis between the intracranial and extracranial circulation, possibly generating an eye unrelated variability in blood flow, we found a trend level reduction of approximately 2 ml/min in NTG. The finding warrants blood flow rate analysis of smaller arteries specifically supplying the eye, e.g. the central retinal artery.
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- Qvarlander, Sara, 1982-, et al.
(författare)
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Differences in cerebral blood flow and CSF flow between INPH and healthy elderly
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Idiopathic normal pressure hydrocephalus (INPH) is linked to disturbance of the CSF circulation, though the exact nature of the disturbance is not clarified. Phase contrast magnetic resonance imaging (PC-MRI) allows for measurement of local CSF and blood flows, and has been applied in hydrocephalus to demonstrate changes in both cerebral blood flow and aqueduct CSF flow. Many of these studies have, however been based on small numbers of subjects, or poorly defined selection criteria. This study therefore aimed to confirm if cerebral blood flow and CSF flow between compartments differed between INPH subjects and healthy elderly.Forty-three healthy elderly and 22 patients diagnosed with INPH according to the INPH guidelines were investigated with PC-MRI measurements of cerebral arterial inflow (CBF) and internal jugular venous outflow, cervical CSF flow, and aqueduct CSF flow. Both net flows, pulsatile aspects of flow, and delays between flow waveforms were analysed.Pulsatility in the aqueduct flow was significantly higher in INPH than healthy elderly (aqueduct stroke volume: 189±184 vs. 86±46 ml, p<0.01). There was larger variation in aqueduct net flow in INPH (SD: 1.31 vs. 0.25 ml/min), but the mean net flow did not differ. Cerebral blood flow and internal jugular vein flow showed no significant differences between the groups, though there was a trend toward lower CBF in the diastolic phase and higher CBF pulsatility index. No differences were found in flow delays.In conclusion, cerebral in- and outflow of blood, and cervical CSF flow were similar in healthy elderly and INPH subjects. Aqueduct flow showed higher pulsatility in INPH, but there was no general reversal of the direction of aqueduct net flow.
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