| 1. |
- 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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| 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. |
- 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. ; 44:8, s. 1343-1351
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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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| 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. |
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| 6. |
- Larsson, Jenny, 1990-
(författare)
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Population-based studies of higher-level gait disorders and hydrocephalus : focused on brain ventricular morphometry and patient outcomes following shunt surgery
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: To study gait is of great importance for the health of the aging population. Higher-level gait disorders (HLGD) are characterized by a slow, symmetrical, unsteady gait. Its cause is most often unknown. HLGD in combination with ventriculomegaly (i.e., large brain ventricles) is obligatory for the diagnosis of Idiopathic Normal pressure hydrocephalus (INPH), a syndrome that is sometimes treatable with insertion of a CSF shunt. It is therefore important to investigate the prevalence of HLGD in the population and brain morphometry in individuals with HLGD. Further, self-perceived confidence in gait and balance among patients with HLGD and INPH is unknown and important to study as slow gait velocity is associated with falls, injuries, and death. CSF shunts in INPH are associated with adverse events and little is known about epilepsy after surgery or minor and moderate adverse events such as headache and abdominal pain.Objective: In the older population investigate the prevalence of HLGD, and its association to ventriculomegaly. To investigate quality of life (QoL), depressive symptoms, and balance confidence in an HLGD population. In patients shunted for INPH, assess falls, fear of falling, balance confidence and prevalence of the possible adverse events headache, epilepsy, and abdominal pain after shunt surgery. Methods: Two population-based case-controlled cohorts were studied. In the first study, the "Ventriculomegaly and gait disturbance in the senior population in the region of Västerbotten" (VESPR) study, individuals (65-84 years) were recruited through a questionnaire (n=6467 dispatched). The final population consisted of 798 cases with gait disorders and 249 controls without gait disorders, age- and sex-matched to individuals with HLGD. All had been examined by a physician and were categorized: 1. "HLGD"; 2. "neurological gait disorder"; 3. "non-neurological gait disorder" or; 4. "no gait disorder". Participants were assessed with: the Swedish modification of the Falls-Efficacy Scale (FES(S)), the Modified Gait-Efficacy Scale (mGES), the Euro Quality of Life 5-Dimension 5-Level (EQ5D5L) instrument (EQ5D5L index and Euro Quality of life visual analogue scale (EQ VAS)) and the Geriatric depression scale 15 (GDS-15). Cases and controls had an MRI of the brain and ventricular size was measured. The second study, the "Comorbidities and vascular risk factors associated with idiopathic normal pressure hydrocephalus" (INPH-CRasH) study, consisted of 176 shunted INPH patients and 368 age- and sex-matched controls. Mean age was 74 years in INPH and 73 in controls. All had a visit to a healthcare facility. Information regarding adverse events, falls and fear of falling were gathered through a questionnaire. Additional information on diagnoses and prescribed drugs were obtained from the Swedish national patient- and drug registries. Data was compared between the groups, and before- and after surgery for INPH. Results: In the VESPR study, 87 individuals were categorized as HLGD, corresponding to a prevalence of 5.8% (95% confidence interval (CI) 4.6-7.0) in the older population. A definite cause was found in 13% (n=11) of individuals with HLGD, but ventriculomegaly was present in 63% (n=46/73, controls: 38%, n=70/184; OR 2.8 95% CI 1.6-4.9, p<0.001). HLGD had more depressive symptoms and lower quality of life (QoL), compared with individuals without gait disorder (GDS-15: 3.9±3.4 vs. 2.5±2.8, p=0.004; EQ VAS: 63±17 vs. 71±18; p<0.001; EQ5D5L index: 0.671±0.188 vs. 0.840±0.126, p<0.001). HLGD had low confidence in gait and to avoid falls compared to those without gait disorder (mGES: 60±22 vs. 74±21; p<0.001; FES(S): 93±32 vs. 111±25 p<0.001). The INPH-CRasH study revealed that patients with INPH feared falling more often (3.3±1.1) and had lower balance confidence (78±40) than controls (fear of falling: 1.6±0.9, balance confidence: 126±14; p<0.001 in both comparisons). After surgery, the proportions were reduced in INPH (p<0.001). More INPH than controls were fallers (before surgery: 67% vs. 11% OR 15.48 95% CI 9.85-24.32; after surgery: 35% vs 11% OR 4.15 95% CI 2.65-6.50, p<0.001). The proportion was reduced after surgery (p<0.001). In shunted INPH, epilepsy, antiepileptic drug (AED) treatment and headache was more common than in controls (epilepsy: 4.5% vs. 1.1% OR 4.3, 95% CI 1.3-14.6, p=0.023; AED treatment: 14.8% vs. 7.3% OR 0.5 95% CI 0.3-0.8, p=0.010; headache: 36.1% vs 11.6% OR 0.2 95% CI 0.2-0.4, p<0.001). Forty percent INPH (n=70) had abdominal pain after surgery. Conclusions: HLGD was common in the general older population and associated to ventriculomegaly. HLGD was also associated with low quality of life and depressive symptoms. Both individuals with HLGD and patients with INPH had low confidence in their balance but it was less common after surgery for INPH. However, patients shunted for INPH still had more problems with low balance confidence, falls, and fear of falling than controls. After shunt surgery for INPH, a significant portion of patients developed epilepsy, headache, and abdominal pain. The findings motivate investigations of causal relationships between HLGD and ventriculomegaly and if treatment options exist for HLGD. The observed adverse events in patients shunted for INPH should be considered in pre- and postoperative evaluations of shunt surgery, and in the development of new techniques for shunt placement. Additional interventions directed towards low balance confidence, falls and fear of falling should be considered for patients with INPH, and for individuals with HLGD.
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| 7. |
- Svantesson, Mats, 1975-
(författare)
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Self-supervised deep learning and EEG categorization
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Deep learning has the potential to be used to improve and streamline EEG analysis. At the present, classifiers and supervised learning dominate the field. Supervised learning depends on target labels which most often are created by human experts manually classifying data. A problem with supervised learning is intra- and interrater agreement which in some instances are far from perfect. This can affect the training and make evaluation more difficult. This thesis includes three papers where self-supervised deep neural networks were developed. In self-supervised learning, the input data to the networks themselves contain structures that are used as targets for the training and no labeling is necessary. In paper I, deep neural networks were trained to increase the number of-, or to recreate missing EEG-channels. The performance was at least on the same level as that of spherical interpolation, but unlike in the case of interpolation, missing data does not have to be identified manually first. Papers II and III involved developing deep neural networks for clustering analysis. The networks produced two-dimensional representations of EEG data and the training strategy was based on the principle of t-distributed stochastic neighbor embedding (t-SNE). In paper II, comparisons were made to parametric t-SNE and EEG-features obtained from time-frequency methods. The deep neural networks produced more distinct clustering when tested on data annotated for epileptiform discharges, seizure activity, or sleep-wakefulness.In paper III, the newly developed method was used to compare annotations of epileptiform discharges. Two experts performed independent annotations and classifiers were trained on these, using supervised learning, which in turn produced new annotations. The agreement when comparing two sets of annotations was not larger between the two experts than between an expert and a classifier. The analysis showed that differences in the annotations by the experts influenced the training of the classifiers. However, the clustering analysis indicated that although it was not always the exact same waveforms that were assessed as epileptiform discharges, they were often similar.The work thus resulted in different methods to process and analyze EEG data, which may have practical usefulness. Traditional agreement scores only assess the exact agreement. However, they reveal nothing about the nature of disagreement. Cluster analysis can provide a means to perform this assessment.
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| 8. |
- 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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| 9. |
- Behrens, Anders, 1979-
(författare)
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Measurements in Idiopathic Normal Pressure Hydrocephalus : Computerized neuropsychological test battery and intracranial pulse waves
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Idiopathic Normal Pressure Hydrocephalus (INPH) is a condition affecting gait, cognition and continence. Radiological examination reveals enlarged ventricles of the brain. A shunt that drains CSF from the ventricles to the abdomen often improves the symptoms. Much research on INPH has been focused on identifying tests that predict the outcome after shunt surgery. As part of this quest, there are attempts to find measurement methods of intracranial parameters that are valid, reliable, tolerable and safe for patients.Today's technologies for intracranial pressure (ICP) measurement are invasive, often requiring a burr-hole in the skull. Recently, a method for non-invasive ICP measurements was suggested: the Pulsatile Index (PI) calculated from transcranial Doppler data assessed from the middle cerebral artery. In this thesis the relation between PI and ICP was explored in INPH patients during controlled ICP regulation by lumbar infusion. The confidence interval for predicted ICP, based on measured PI was too large for the method to be of clinical utility.In the quest for better predictive tests for shunt success in INPH, recent studies have shown promising results with criteria based on cardiac related ICP wave amplitudes. The brain ventricular system, and the fluid surrounding the spinal cord are in contact. In this thesis it was shown that ICP waves could be measured via lumbar subarachnoid space, with a slight underestimation.One of the cardinal symptoms of hydrocephalus is cognitive impairment. Neuropsychological studies have demonstrated cognitive tests that are impaired and improve after shunt surgery in INPH patients. However, there is currently no standardized test battery and different studies use different tests. In response, in this thesis a fully automated computerized neuropsychological test battery was developed. The validity, reliability, responsiveness to improvement after shunt surgery and feasibility for testing INPH patients was demonstrated. It was also demonstrated that INPH patients were impaired in all subtests, compared to healthy elderly.
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| 10. |
- Björnfot, Cecilia, et al.
(författare)
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Assessing cerebral arterial pulse wave velocity using 4D flow MRI
- 2021
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016. ; 41:10, s. 2769-2777
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Tidskriftsartikel (refereegranskat)abstract
- Intracranial arterial stiffening is a potential early marker of emerging cerebrovascular dysfunction and could be mechanistically involved in disease processes detrimental to brain function via several pathways. A prominent consequence of arterial wall stiffening is the increased velocity at which the systolic pressure pulse wave propagates through the vasculature. Previous non-invasive measurements of the pulse wave propagation have been performed on the aorta or extracranial arteries with results linking increased pulse wave velocity to brain pathology. However, there is a lack of intracranial “target-organ” measurements. Here we present a 4D flow MRI method to estimate pulse wave velocity in the intracranial vascular tree. The method utilizes the full detectable branching structure of the cerebral vascular tree in an optimization framework that exploits small temporal shifts that exists between waveforms sampled at varying depths in the vasculature. The method is shown to be stable in an internal consistency test, and of sufficient sensitivity to robustly detect age-related increases in intracranial pulse wave velocity.
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