| 1. |
- Jóhannesson, Gauti, 1979-
(författare)
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Intraocular pressure : clinical aspects and new measurement methods
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Intraocular pressure (IOP) measurement is a routine procedure and a fundament in glaucoma care. Elevated IOP is the main risk factor for glaucoma, and to date, reduction of IOP is the only possible treatment. In a retrospective clinical material, the prevalence of open angle glaucoma was estimated on the west coast of Iceland. IOP measurement and optic nerve head examination were used to capture glaucoma suspects, within the compulsory ophthalmological examination for the prescription of eye glasses. The results were mainly in agreement with a recent prospective study in the same region. This indicated that retrospective data, under certain conditions, may contribute with useful information on the prevalence of glaucoma. However, normal tension glaucoma is underestimated if perimetry and/or fundus photography are not included in the examination. Three studies focused on the measurement of IOP. Goldmann applanation tonometry (GAT) is the standard method. GAT is affected by corneal properties, e.g. central corneal thickness (CCT) and corneal curvature (CC). Refractive surgery changes these properties. This has put focus on how corneal biomechanics translate into tonometric errors and stimulated the development of new methods. As a result, Pascal ® Dynamic Contour Tonometry (PDCT) and Icare® rebound tonometry have been introduced. A method under development by our research group is Applanation Resonance Tonometry (ART). It is based on resonance technology and estimates IOP from continuous measurement of force and contact area. Comparison of PDCT, Icare and GAT in a prospective study showed that the concordance to GAT was close to the limits set by the International Standard Organization (ISO) for PDCT, while Icare was outside the limits. To investigate if laser-assisted subepithelial keratectomy (LASEK) affects tonometry, a study was performed where measurements with GAT, PDCT and ART were obtained before, three and six months after LASEK. The hypothesis was that PDCT and ART would be less affected by LASEK than GAT. The results showed a statistically significant reduction of measured IOP three and six months after LASEK for all tonometry methods. Change in visual acuity and IOP between three and six months suggested a prolonged postoperative process. A servo-controlled prototype (ART servo) was developed. A study was undertaken to assess the agreement of ARTservo and a further developed v manual prototype (ART manual) with GAT. The study design was in accordance with the requirements of the ISO standard for tonometers. ARTmanual fulfilled the precision requirements of the ISO standard. ARTservo did not meet all the requirements of the standard at the highest pressure levels. Four tonometry methods, GAT, PDCT, Icare and ART, were investigated. None of them was independent of both CCT and CC. The inconsistencies in the results emphasize the importance of study design. A meta-analysis comprising healthy eyes (IOP ≤ 21 mmHg) in the three papers, revealed age as an important confounder. In summary, glaucoma prevalence in Iceland was investigated and the results indicated that a retrospective approach can contribute with meaningful information. ART and PDCT had a similar agreement to GAT. ART manual fulfilled the precision requirements set by the ISO-standard, ARTservo and PDCT were close, while Icare was distinctly outside the limits. All tonometry methods were affected by LASEK and no method was completely independent of corneal properties.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- Lenfeldt, Niklas, 1972-
(författare)
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The search for reversibility of Idiopathic normal pressure hydrocephalus : Aspects on intracranial pressure measurments and CSF volume alteration
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Idiopathic normal pressure hydrocephalus (INPH) is still a syndrome generating more questions than answers. Today, research focuses mainly on two areas: understanding the pathophysiology – especially how the malfunctioning CSF system affects the brain parenchyma – and finding better methods to select patients benefiting from a shunt operation.This thesis targets the aspect of finding better selection methods by investigating the measurability of intracranial pressure via lumbar space, and determining if intraparenchymal measurement of long-term ICP-oscillations (B-waves) could be replaced by short-term measurements of CSF pulse pressure waves via lumbar space. Furthermore, I look into the interaction between the CSF system and the parenchyma itself by investigating how the cortical activity of the brain changes after long-term CSF drainage, and if there is any regress in the suggested ischemia after this intervention. Finally, I examine if the neuronal integrity in the INPH brain is impaired, and if this feature is relevant for the likeliness of improvement after CSF diversion.METHODS: The comparison of intracranial and lumbar pressure was made over a vast pressure interval using our unique CSF infusion technique, and it included ten INPH patients. Pressure was measured via lumbar space and in brain tissue, and the pressures were compared using a general linear model. Short-term lumbar pressure waves were quantified by determining the slope between CSF pulse pressure and mean pressure, defined as the relative pulse pressure coefficient (RPPC). The correlation between RPPC, B-waves and CSF outflow resistance was investigated.In a prospective study, functional MRI was used to assess brain activity before and after long-term CSF drainage of 400 ml of CSF in eleven INPH patients. The functionalities tested included finger movement, memory, and attention. The results were benchmarked against the activity in ten healthy controls to identify the brain areas improving after drainage. The ischemia (Lactate) and neuronal integrity (NAA and Choline) were measured in a similar manner in 16 patients using proton MR spectroscopy, and the improvement of the patients after CSF drainage was based on assessment of their gait.RESULTS: There was excellent agreement between ICP measured in brain tissue and via lumbar space (regression coefficient = 0.98, absolute difference < 1 mm Hg). Adjusting for the separation distance between the measuring devices slightly worsened the agreement, indicating other factors influencing the measured difference as well. RPPC measured via lumbar space significantly correlated to the presence of B-waves, but not to outflow resistance.In the prospective study, controls outperformed patients on clinical tests as well as tasks related to the experiments. Improved behaviour after CSF drainage was found for motor function only, and it was accompanied by increased activation in the supplementary motor area (SMA). No lactate was detected, either before or after CSF drainage. NAA was decreased in INPH patients compared to controls, and the NAA levels were higher in the patients improving after drainage.CONCLUSIONS: ICP can be accurately measured via lumbar space in patients with communicating CSF systems. The close relation between RPPC and B-waves indicates that B-waves are primarily related to intracranial compliance, and that measurement of RPPC via lumbar space could possibly substitute B-wave assessment as selection method for finding suitable patients for shunt surgery.Improvement in motor function after CSF drainage was associated to enhanced activity in SMA, supporting the involvement of the cortico-basal ganglia-thalamo-cortical loop in the pathophysiology of INPH. There was no evidence indicating a widespread low-graded ischemia in INPH; however, there was a neuronal dysfunction in frontal white matter as indicated by the reduced levels of NAA. In addition, the level of neuronal dysfunction was related to the likeliness of improvement after CSF removal, normal levels of NAA predisposing for recovery.
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| 6. |
- Ljubimova, Darja, 1981-
(författare)
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Biomechanics of the Human Eye and Intraocular Pressure Measurements
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis addresses the reliability of Goldmann-type applanation tonometers (GAT). It deals with the investigation of the relation between predicted intraocular pressure, IOPG and true pressure, IOPT. The problem of the accuracy of GAT readings has acquired special importance over the last two decades as new types of surgical procedures to correct vision disorders are being explored and gain universal acceptance. The overall aim of the present study is to assess the effects of individual variations in the corneal central thickness (CCT), material properties of the involved tissues and paracentral applanation on the accuracy of IOPG. Two finite element models have been constructed: a two-dimensional axisymmetric model of the cornea and a three-dimensional model of the whole corneoscleral envelope. Various material descriptions were adopted for the cornea in 2D, whereas the 3D model accounted for collagen microstructure and represented a hyperelastic ber reinforced material. Nonlinear analyses were carried out using the commercial general-purpose finite element software ABAQUS. An extensive literature survey and consultations with ophthalmologists and clinicians were the platform for establishing relevant modelling procedures. The results reveal a clear association between all considered parameters and measured IOPG. The effect of assumed CCT is highly dependent on the corneal material properties. Material model alone has a profound effect on predicted IOPG. Variations in tonometer tip application produce clinically signi cant errors to IOPG measurements. Potential effects of corneal stiffness and paracentral applanation on GAT readings are larger than the impact of CCT. The behaviour of the models is broadly in agreement with published observations. The proposed procedures can be a useful tools for suggesting the magnitudes of corrections for corneal biomechanics and possible human errors. The present modelling exercise has an ability to reproduce the behaviour of human cornea and trace it under IOP and GAT, providing potentially useful information on the distribution of stresses and strains. Some recommendations can be drawn in pursuit of the clinical imperatives of ophthalmologists.
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| 7. |
- Vikner, Tomas, 1990-
(författare)
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Cerebral arterial pulsatility imaging using 4D flow MRI : methodological development and applications in brain aging
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 4D flow magnetic resonance imaging (MRI) is increasingly recognizedas a versatile tool to assess arterial and venous hemodynamics. Cerebral arterial pulsatility is typically assessed by analyzing flow waveforms over the cardiac cycle, where flow amplitude is a function of cardiac output, central arterial stiffness, and cerebrovascular resistance and compliance. Excessive pulsatility may propagate to the cerebral microcirculation, and constitute a harmful mechanism for the brain. Indeed, imaging studies have linked arterial pulsatility to hippocampus volume, cerebral small vessel disease (SVD), and Alzheimer’s disease (AD). In animal models, elevated pulsatility leads to blood-brain barrier (BBB) leakage, capillary loss, and cognitive decline. However, associations to cerebrovascular lesions and brain function in the spectrum of normal aging are less investigated. Further, previous 4D flow studies have mainly assessed pulsatility in relatively large cerebral arteries. When exploring links to microvascular damage and brain function, more distal measurements, closer to the microcirculation, are desired. This thesis aimed to develop 4D flow MRI post-processing methods to obtain pulsatile waveforms in small, distal cerebral arteries with noisy velocity data and a complex vascular anatomy, and to evaluate pulsatility (primarily assessed by the pulsatility index) in relation to aging, brain function, and other imaging biomarkers of cerebrovascular damage, with particular dedication towards the hippocampus and cerebral SVD. To assess pulsatility in distal cerebral arteries, a post-processing method that automatically samples waveforms from numerous small arteries, to obtain a whole-brain representation of the distal arterial waveform, was developed (Paper I). We demonstrated the importance of averaging flow waveforms along multiple vessel segments to avoid overestimations in the pulsatility index, showed agreement with reference methods, and linked distal arterial pulsatility to age. To explore links to hippocampal function, we evaluated pulsatility in relation to cognition, hemodynamic low-frequency oscillations (LFOs), perfusion, and hippocampus volume (Paper II). We found that higher pulsatility was linked to worse hippocampus-sensitive episodic memory, weaker hippocampal LFOs, and lower whole-brain perfusion. These findings aligned with models suggesting that hippocampal microvessels could be particularly susceptible to pulsatile stress.To inform on SVD pathophysiology, we evaluated 5-year associations among pulsatility, white matter lesions (WMLs) and perivascular space (PVS) dilation, using mixed models, factor analysis, and change score models (Paper III). Lead-lag analyses indicated that, while pulsatility at baseline could not predict WML nor PVS progression, WML and PVS volumes at baseline predicted 5-year pulsatility-increases. These findings indicate that individuals with a higher load of cerebrovascular damage are more prone to see increased pulsatility over time, and suggest that high pulsatility is a manifestation, rather a risk factor, for cerebral SVD. To shed light on the potential role of BBB leakage in aging and SVD, we used dynamic contrast enhanced (DCE) MRI and intravenous gadolinium injections to quantify BBB permeability (Paper IV). We found stepwise increases in permeability from healthy white matter to WMLs, supporting that BBB leakages are implicated in SVD. However, hippocampal BBB permeability was unrelated to age, indicating that this capillary property is maintained in aging. Finally, arterial pulsatility was unrelated to BBB permeability in WMLs and in the hippocampus, providing no evidence of excessive pulsatility as a trigger of BBB leakage. In conclusion, distal arterial pulsatility measurements are reliable when averaging 4D flow waveforms over a large number of vessels. Pulsatility increases with age, and individuals with more cerebrovascular lesions are prone to see larger increases over time. Pulsatility is negatively related to perfusion and hippocampal function. However, the temporal dynamics among the SVD biomarkers, and the absence of pulsatility–permeability associations, challenge the concept of excessive pulsatility as a trigger of microvascular damage. Future studies are needed to understand whether altered cerebral hemodynamics play a causal role in cognitive decline and dementia. Meanwhile, 4D flow hemodynamic parameters could be useful as biomarkers related to vessel properties and cerebrovascular health.
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| 8. |
- Wåhlin, Anders, 1983-
(författare)
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Cerebral blood flow and intracranial pulsatility studied with MRI : measurement, physiological and pathophysiological aspects
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During each cardiac cycle pulsatile arterial blood inflates the vascular bed of the brain, forcing cerebrospinal fluid (CSF) and venous blood out of the cranium. Excessive arterial pulsatility may be part of a harmful mechanism causing cognitive decline among elderly. Additionally, restricted venous flow from the brain is suggested as the cause of multiple sclerosis. Addressing hypotheses derived from these observations requires accurate and reliable investigational methods. This work focused on assessing the pulsatile waveform of cerebral arterial, venous and CSF flows. The overall aim of this dissertation was to explore cerebral blood flow and intracranial pulsatility using MRI, with respect to measurement, physiological and pathophysiological aspects. Two-dimensional phase contrast magnetic resonance imaging (2D PCMRI) was used to assess the pulsatile waveforms of cerebral arterial, venous and CSF flow. The repeatability was assessed in healthy young subjects. The 2D PCMRI measurements of cerebral arterial, venous and CSF pulsatility were generally repeatable but the pulsatility decreased systematically during the investigation. A method combining 2D PCMRI measurements with invasive CSF infusion tests to determine the magnitude and distribution of compliance within the craniospinal system was developed and applied in a group of healthy elderly. The intracranial space contained approximately two thirds of the total craniospinal compliance. The magnitude of craniospinal compliance was less than suggested in previous studies. The vascular hypothesis for multiple sclerosis was tested. Venous drainage in the internal jugular veins was compared between healthy controls and multiple sclerosis patients using 2D PCMRI. For both groups, a great variability in the internal jugular flow was observed but no pattern specific to multiple sclerosis could be found. Relationships between regional brain volumes and potential biomarkers of intracranial cardiac-related pulsatile stress were assessed in healthy elderly. The biomarkers were extracted from invasive CSF pressure measurements as well as 2D PCMRI acquisitions. The volumes of temporal cortex, frontal cortex and hippocampus were negatively related to the magnitude of cardiac-related intracranial pulsatility. Finally, a potentially improved workflow to assess the volume of arterial pulsatility using time resolved, four-dimensional phase contrast MRI measurements (4D PCMRI) was evaluated. The measurements showed good agreement with 2D PCMRI acquisitions. In conclusion, this work showed that 2D PCMRI is a feasible tool to study the pulsatile waveforms of cerebral blood and CSF flow. Conventional views regarding the magnitude and distribution of craniospinal compliance was challenged, with important implications regarding the understanding of how intracranial vascular pulsatility is absorbed. A first counterpoint to previous near-uniform observations of obstructions in the internal jugular veins in multiple sclerosis was provided. It was demonstrated that large cardiac- related intracranial pulsatility were related to smaller volumes of brain regions that are important in neurodegenerative diseases among elderly. This represents a strong rationale to further investigate the role of excessive intracranial pulsatility in cognitive impairment and dementia. For that work, 4D PCMRI will facilitate an effective analysis of cerebral blood flow and pulsatility.
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| 9. |
- Andersson, Kennet, 1979-
(författare)
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Assessment of cerebrospinal fluid system dynamics : novel infusion protocol, mathematical modelling and parameter estimation for hydrocephalus investigations
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients with idiopathic normal pressure hydrocephalus (INPH) have a disturbance in the cerebrospinal fluid (CSF) system. The treatment is neurosurgical – a shunt is placed in the CSF system. The infusion test is used to assess CSF system dynamics and to aid in the selection of patients that will benefit from shunt surgery. The infusion test can be divided into three parts: a mathematical model, an infusion protocol and a parameter estimation method. A non-linear differential equation is used to mathematically describe the CSF system, where two important parameters are the outflow conductance (Cout) and the Pressure Volume Index (PVI). These are used both for clinical and research purposes. The analysis methods for the non-linear CSF system have limited the infusion protocols of presently used infusion investigations. They come with disadvantages such as long investigation time, no estimation of PVI and no measure of the reliability of the estimates.The aim of this dissertation was to develop and evaluate novel methods for infusion protocols, mathematical modelling and parameter estimation methods for assessment of CSF system dynamics.The infusion protocols and parameter estimation methods in current use, constant pressure infusion (CPI), constant infusion and bolus infusion, were investigated. The estimates of Cout were compared, both on an experimental set-up and on 20 INPH patients. The results showed that the bolus method produced a significantly higher Cout than the other methods. The study suggested a method with continuous infusion for estimating Cout and emphasized that standardization of Cout measurement is necessary.The non-linear model of the CSF system was further developed. The ability to model physiological variations that affect the CSF system was incorporated into the model and it was transformed into a linear time-invariant system. This enabled the use of methods developed for identification of such systems. The underlying model for CSF absorption was discussed and the effect of baseline resting pressure (Pr) in the analysis on the estimation of Cout was explored using two different analyses, with and without Pr.A novel infusion protocol with an oscillating pressure pattern was introduced. This protocol was theoretically better suited for the CSF system characteristics. Three new parameter estimation methods were developed. The adaptive observer was developed from the original non-linear model of the CSF system and estimated Cout in real time. The prediction error method (PEM) and the robust simulation error (RSE) method were based on the transformed linear system, and they estimated both Cout and PVI with confidence intervals in real time. Both the oscillating pressure pattern and the reference CPI protocol were performed on an experimental set-up of the CSF system and on 47 hydrocephalus patients. The parameter estimation methods were applied to the data, and the RSE method produced estimates of Cout that were in good agreement with the reference method and allowed for an individualized and considerably reduced investigation time.In summary, current methods have been investigated and a novel approach for assessment of CSF system dynamics has been presented. The Oscillating Pressure Infusion method, which includes a new infusion protocol, a further developed mathematical model and new parameter estimation methods has resulted in an improved way to perform infusion investigations and should be used when assessing CSF system dynamics. The advantages of the new approach are the pressure-regulated infusion protocol, simultaneous estimation of Cout and PVI and estimates of reliability that allow for an individualized investigation time.
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| 10. |
- Gu, Xuan, 1988-
(författare)
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Advanced analysis of diffusion MRI data
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diffusion magnetic resonance imaging (diffusion MRI) is a non-invasive imaging modality which can measure diffusion of water molecules, by making the MRI acquisition sensitive to diffusion. Diffusion MRI provides unique possibilities to study structural connectivity of the human brain, e.g. how the white matter connects different parts of the brain. Diffusion MRI enables a range of tools that permit qualitative and quantitative assessments of many neurological disorders, such as stroke and Parkinson.This thesis introduces novel methods for diffusion MRI data analysis. Prior to estimating a diffusion model in each location (voxel) of the brain, the diffusion data needs to be preprocessed to correct for geometric distortions and head motion. A deep learning approach to synthesize diffusion scalar maps from a T1-weighted MR image is proposed, and it is shown that the distortion-free synthesized images can be used for distortion correction. An evaluation, involving both simulated data and real data, of six methods for susceptibility distortion correction is also presented in this thesis.A common problem in diffusion MRI is to estimate the uncertainty of a diffusion model. An empirical evaluation of tractography, a technique that permits reconstruction of white matter pathways in the human brain, is presented in this thesis. The evaluation is based on analyzing 32 diffusion datasets from a single healthy subject, to study how reliable tractography is. In most cases only a single dataset is available for each subject. This thesis presents methods based on frequentistic (bootstrap) as well as Bayesian inference, which can provide uncertainty estimates when only a single dataset is available. These uncertainty measures can then, for example, be used in a group analysis to downweight subjects with a higher uncertainty.
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