| 1. |
- Sandstedt, Mårten, 1972-
(author)
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Computed Tomography of the Coronary Arteries : Developmental and Prognostic Investigations
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Computed tomography (CT) is an increasingly used modality for investigations of patients with suspected coronary artery disease (CAD). Technical advances could improve diagnostic accuracy and lead to clinical workflow improvements. Also, more prognostic information can optimize clinical follow-up strategies and treatments.The general aim of this thesis was to explore the use of CT for CAD investigations. Three studies aimed to examine new technologies, including the evaluation of an on-site, computed tomography-based fractional flow reserve (CT-FFR) software (study I), the evaluation of an AI-based, calcium scoring computed tomography (CSCT) software (study III), and the evaluation of an photon-counting detector (PCD)-CT (study IV). One study aimed to evaluate the long-term prognostic value of coronary computed tomography angiography (CCTA) in symptomatic patients with no history of CAD (study II).The software evaluation studies (study I and III) and the prognostic study (study II) utilized CT data from clinical patients, while the PCD-CT evaluation study (study IV) used CT data from cadaveric specimens. The performances of both software programs were compared with standard references, being represented by fractional flow reserve (FFR) measurements (study I), and coronary artery calcification (CAC) scores from a semi-automatic software (study III), respectively. The PCD-CT performance on CAC quantification was compared with corresponding results from an energy integrating detector (EID)-CT, using micro-CT as the standard reference (study IV). The prognostic study merged registries to identify major adverse cardiac events (MACE), having a follow-up time of up to 7.5 years (study II).The CT-FFR and CSCT software correlation and agreement to corresponding standard references were good and excellent, respectively. Also, both software programs had time-saving potential (study I and III). The CAC quantification was more accurate using PCD-CT than EID-CT (study IV). The prognosis was excellent in patients with normal coronary arteries, and progressively impaired in non-obstructive and obstructive CAD (study II).The results in this thesis convey developmental, technical CT technology advances for CAD investigations. In addition, prognostic follow-up data is communicated. The results may benefit patients by an increased accuracy in the CT evaluation of CAD and can contribute to improve clinical follow-up strategies. Furthermore, the results suggest possibilities to improve the workflow in clinical radiology, which potentially could impact health care costs.
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| 2. |
- Grönberg, Fredrik
(author)
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Spectral Photon-Counting Computed Tomography with Silicon Detectors: New Models and Applications
- 2022
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Doctoral thesis (other academic/artistic)abstract
- X-ray computed tomography (CT) is a widely used imaging modality that enables visualization of nearly every part of the human body. It is used for diagnosis of disease and injury as well as medical treatment planning. The vast majority of CT scanners in clinical use today have energy-integrating x-ray detectors, which measure the total incident energy in a given measurement.Spectral photon-counting detectors operate by counting individual photons and measuring their energy, and are expected to yield the next major advance in CT, with improvements in spatial resolution, dose efficiency, material differentiation and quantitative imaging capabilities compared to the current state-of-the-art.In this Thesis, a set of new models and applications for a spectral photon-counting silicon detector developed for CT is investigated. The first part of the Thesis is dedicated to the modeling of spectral photon-counting silicon detectors. A new statistical model for the effects of pulse pileup is presented. Also, the effects on image quality from intra-detector Compton scatter in silicon detectors are investigated via spatio-energetic modeling. In the second part of the Thesis, potential applications for spectral photon-counting detectors are investigated. An experimental study of ex vivo CT imaging of an excised human heart with calcified plaque is presented. It demonstrates the feasibility of unconstrained projection-based three-material decomposition with iodine as a third basis material and explores the potential improvements in spatial resolution and material differentiation that can be achieved with a spectral photon-counting silicon detector compared to a conventional dual-energy CTsystem. Two other applications are investigated with simulations: a method for reconstructing CT images from spectral photon-counting CT data that accurately mimic conventional CT images; and a method for estimating iron concentration in mixtures of liver and adipose tissue when using three basis functions instead of only two to describe the linear attenuation coefficient of tissues in the human body. Although the methods presented in this Thesis have been specifically developed for a spectral photon-counting silicon detector, they are also applicable for other types of photon-counting detectors.
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| 3. |
- Bergström, Göran, 1964, et al.
(author)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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In: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Journal article (peer-reviewed)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 4. |
- Frölich, Emilia, 1982-
(author)
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Från Kingston till Göinge : autencitet, identitet och representationer av det förflutna i svensk reggaekultur
- 2022
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Doctoral thesis (other academic/artistic)abstract
- This thesis explores the role of history in popular culture with a particular focus on the Swedish reggae scene. It examines how cultural meaning applied to music bears strong connections to historical representations, and how individuals understand, communicate, and reproduce selective notions of the past in relationship to popular music. History is viewed as an essential cultural component in this thesis, a component equipped with the ability to articulate political resistance, and express a sense of identity and belonging. The overall purpose is to examine how history is constructed, represented and used in the Swedish reggae scene, and how notions of origin and authenticity are expressed. The empirical chapters examine how different representations of the past in Swedish reggae relates to notions of origin, place and authenticity. These representations are constructed through social interactions, but also through interaction with texts, objects, and cultural practices.As the thesis shows, different representations of pasts and notions of origins exists in Swedish reggae, connecting to various geographical, cultural, and historical contexts. The hybridization of reggae becomes an important factor that contributes to making Swedish reggae something special and unique. In the Swedish reggae scene, which is predominatly white, the hybridization can be understood as an attempt to free oneself from aspects of reggae associated with Black experiences of white oppression. The use of local, regional, and national cultural expressions and representations of the past creates a distance to the Jamaican reggae traditions, and the historical narratives of slavery, colonialism and racial discrimination that reinforces the Black identification in Jamaican reggae. Instead, by relating to Swedish historical milieus, traditions and events, a closer and more relatable understanding of reggae is created. However, the thesis also shows that not all actors who consume and produce reggae in Sweden identify with the Swedish hybrid version. In such cases, its typical Swedishness is seen as an undesirable departure from the history and traditions of Jamaican reggae. Jamaican reggae is then perceived as a cultural heritage that should be preserved and respected in its original form - not in a copied or remodelled version.
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| 5. |
- Hall, Emma
(author)
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Mellan rörelse och stillhet : minne och flykt i unga människors berättande 2009-2021.
- 2023
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Doctoral thesis (other academic/artistic)abstract
- The purpose of this thesis is to highlight young people’s experiences of forced migration along irregular migration routes and to examine how they understand themselves in relation to different contexts in time and space. The participants consist of young people with experience of forced migration and of being categorized as ”ensamkommande barn” (unaccompanied minors) upon arrival in Sweden. Using oral and written sources, the thesis explores what and how they remember. The theoretical perspectives are connected by movement as an overarching metaphor. Movement refers to the physical movements made by the participants as well as the assumption that movement characterizes the process of remembering. This is connected to oral history theory and method and the exploration of the past as well as the relationship between past and present in everyday lives. The thesis also leans on several theoretical perspectives from cultural memory studies, which highlight the process in which an individual memory is shaped and reshaped depending on social context and over time. In order to explore how the participants remember different places and times, from origin to destination, a systems approach to migrant trajectories has been applied as a heuristic tool.The analysis shows that there are shared historical contexts despite the fact that the participants make a heterogenous group. During the period of investigation, migration to and within Europe has been characterized by restrictions and control. This means that the participants have travelled via irregular routes, and they have been confronted with strict border controls. When the participants arrived in Sweden, migration policy underwent significant changes that led to consequences for the participants themselves. Furthermore, those labelled ”ensamkommande barn” were at the center of the migration policy debate in the wake of the so called ”refugee crisis” in 2015. An important conclusion in this dissertation is that to a large extent, movements in time and space have led to a development of how the participants understand themselves. In addition to movements over time, shifts in social contexts bring changes to what and how the participants remember. To conclude, this thesis contributes to research on ”ensamkommande barn” as it illuminates the different ways in which the participants understand themselves and experience a sense of belonging. Another contribution is the thesis' approach to historical contextualization and the understanding of the participants as actors in relation to larger historical change.
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| 6. |
- Oldgren, Jonas, 1964-, et al.
(author)
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Systematic Coronary Risk Evaluation estimated risk and prevalent subclinical atherosclerosis in coronary and carotid arteries: A population-based cohort analysis from the Swedish Cardiopulmonary Bioimage Study
- 2021
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In: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 28:3, s. 250-259
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Journal article (peer-reviewed)abstract
- Background It is not clear if the European Systematic Coronary Risk Evaluation algorithm is useful for identifying prevalent subclinical atherosclerosis in a population of apparently healthy individuals. Our aim was to explore the association between the risk estimates from Systematic Coronary Risk Evaluation and prevalent subclinical atherosclerosis. Design The design of this study was as a cross-sectional analysis from a population-based study cohort. Methods From the general population, the Swedish Cardiopulmonary Bioimage Study randomly invited individuals aged 50-64 years and enrolled 13,411 participants mean age 57 (standard deviation 4.3) years; 46% males between November 2013-December 2016. Associations between Systematic Coronary Risk Evaluation risk estimates and coronary artery calcification and plaques in the carotid arteries by using imaging data from a computed tomography of the heart and ultrasonography of the carotid arteries were examined. Results Coronary calcification was present in 39.5% and carotid plaque in 56.0%. In men, coronary artery calcium score >0 ranged from 40.7-65.9% and presence of carotid plaques from 54.5% to 72.8% in the age group 50-54 and 60-65 years, respectively. In women, the corresponding difference was from 17.1-38.9% and from 41.0-58.4%. A doubling of Systematic Coronary Risk Evaluation was associated with an increased probability to have coronary artery calcium score >0 (odds ratio: 2.18 (95% confidence interval 2.07-2.30)) and to have >1 carotid plaques (1.67 (1.61-1.74)). Conclusion Systematic Coronary Risk Evaluation estimated risk is associated with prevalent subclinical atherosclerosis in two major vascular beds in a general population sample without established cardiovascular disease or diabetes mellitus. Thus, the Systematic Coronary Risk Evaluation risk chart may be of use for estimating the risk of subclinical atherosclerosis.
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| 7. |
- Persson Skare, Tor
(author)
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Investigating histidine-rich glycoprotein and T cell-specific adaptor as potential biomarkers and therapeutic targets
- 2021
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Doctoral thesis (other academic/artistic)abstract
- The endothelial cell (EC), the most important cell type in blood vessels, lines the vessel wall and provides vessel integrity. EC function is tightly regulated, and its dysregulation is a key element in many diseases including cardiovascular disease, cancer and several diseases of the eye. This thesis investigates the prognostic and therapeutic potential of two proteins: histidine-rich glycoprotein (HRG) and T cell-specific adaptor protein (TSAd). HRG is an abundant hepatocyte-derived protein, involved in many biological processes including hemostasis and fibrinolysis, inflammation, and angiogenesis. TSAd is an adapter protein downstream of vascular endothelial growth factor (VEGF) receptor 2, required for VEGF-A induced vascular permeability. In Paper I HRG-based therapy is tested in glioma using an HRG-encoding non-replicating adenovirus vector delivered orthotopically in the GL261 mouse glioma model. HRG treatment results in reduced tumor growth and increased vessel perfusion. Further mechanistic analysis reveals that stanniocalcin 2 (STC2) is a binding partner of HRG on the surface of inflammatory cells. Paper II investigates the potential of HRG as a prognostic biomarker in mature B cell lymphomas using tissue microarrays of human lymphoma samples. RNAscope is employed to identify tumor cell expression of HRG, and complementing immunostainings reveal that high HRG expression is a marker of improved overall survival for patients with marginal zone lymphoma, independent of age, stage and sex. In Paper III the interaction of HRG and STC2 is characterized further using the human histiocytic lymphoma cell line U937 that can differentiate towards a macrophage-like cell type after stimulation with vitamin D3. The bioactivity of recombinant HRG and STC2 is ensured by testing their effects on phagocytosis in U937 cells. Quartz crystal microbalance analysis reveals that HRG binds STC2 with high affinity in a conformation dependent manner. Paper IV describes a high throughput screen for a small chemical compound capable of blocking VEGF-induced vascular permeability by binding TSAd. Screening of approximately 22000 compounds results in the discovery of a lead compound that binds TSAd and blocks VEGF-induced permeability in an ex-vivo assay.In summary, the papers presented in this thesis describe different strategies to investigate the role of HRG and TSAd on ECs and how this information can be applied therapeutically. The results confirm the importance of EC biology in disease, and the clinical potential HRG and TSAd as therapeutics or as biomarkers.
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| 8. |
- Brunskog, Rickard, et al.
(author)
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Experimental Evaluation of a Micron-Resolution CT Detector
- 2024
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In: Medical Imaging 2024: Physics of Medical Imaging. - : SPIE-Intl Soc Optical Eng.
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Conference paper (peer-reviewed)abstract
- Purpose: Current photon-counting detectors are limited to a pixel size of 0.3 mm-1 mm, as decreasing the pixel size further generally introduces degraded dose efficiency and energy resolution from excessive charge sharing. In this work, we present experimental measurements of the first photon-counting detector prototype designed to leverage the charge sharing to estimate the photon interaction position, where simulations indicate a theoretical resolution of around 1 µm using a similar geometry. The goal of the measurements is to validate our Monte-Carlo simulation for further development. Approach: DAC sweeps are performed with an X-ray beam at specified locations on the sensor front, with the beam at 20 keV and 35 keV, as well as with different sensor biases with the beam at 35 keV. The experimental data are then compared to a Monte Carlo simulation combined with a charge transport model. In this first prototype wire bonds are used, and as such only a few channels are connected. Results: The experimental data agree generally well with the simulated data with the beam close to the electrodes, with the simulated data diverging from the experiments with the beam further away from the electrodes. The induced charge cloud signal exhibits a fairly linear dependency on the beam position, indicating that any estimation techniques will yield more precise position when the photon interacts further away from the electrodes, rather than closer. Conclusions: With the experimental data and the simulations agreeing generally well, together with the same software previously indicating a resolution of around 1 µm, we expect an ultra-high-resolution detector to be in reach, and are encouraged to continue development.
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| 9. |
- Brunskog, Rickard, et al.
(author)
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First experimental evaluation of a high-resolution deep silicon photon-counting sensor
- 2024
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In: Journal of Medical Imaging. - : SPIE-Intl Soc Optical Eng. - 2329-4302 .- 2329-4310. ; 11:1
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Journal article (peer-reviewed)abstract
- Purpose: Current photon-counting computed tomography detectors are limited to a pixel size of around 0.3 to 0.5 mm due to excessive charge sharing degrading the dose efficiency and energy resolution as the pixels become smaller. In this work, we present measurements of a prototype photon-counting detector that leverages the charge sharing to reach a theoretical sub-pixel resolution in the order of 1 μm. The goal of the study is to validate our Monte-Carlo simulation using measurements, enabling further development. Approach: We measure the channel response at the MAX IV Lab, in the DanMAX beamline, with a 35 keV photon beam, and compare the measurements with a 2D Monte Carlo simulation combined with a charge transport model. Only a few channels on the prototype are connected to keep the number of wire bonds low. Results: The measurements agree generally well with the simulations with the beam close to the electrodes but diverge as the beam is moved further away. The induced charge cloud signals also seem to increase linearly as the beam is moved away from the electrodes. Conclusions: The agreement between measurements and simulations indicates that the Monte-Carlo simulation can accurately model the channel response of the detector with the photon interactions close to the electrodes, which indicates that the unconnected electrodes introduce unwanted effects that need to be further explored. With the same Monte-Carlo simulation previously indicating a resolution of around 1 μm with similar geometry, the results are promising that an ultra-high resolution detector is not far in the future.
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| 10. |
- Daniel, Maxime, et al.
(author)
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Charge collection efficiency of CdTe detectors : Impact of charge collection time and polarisation
- 2023
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In: Medical Imaging 2023. - : SPIE-Intl Soc Optical Eng.
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Conference paper (peer-reviewed)abstract
- Cadmium telluride (CdTe) is one of the materials used in photon-counting detectors for x-ray computed tomography. One challenge with this material is that it is susceptible to polarisation due to holes being trapped in impurities in the material. This can potentially lead to the buildup of bulk charge in the semiconductor, causing decreased charge collection efficiency and degraded energy resolution. In this work, we develop a simulation model of CdTe detectors with polarisation and use it to study the effect of polarisation on the measured energy spectrum for different charge collection times. To this end, we use a theoretical model of charge buildup to find the critical charge in the detector's bulk above which the detector can be considered completely polarised. We then simulate a 320-by-270-by-1600 μm CdTe detector used in CT clinical imaging, for varying degrees of polarisation (ratio between the actual charge and the critical charge) and charge collection time. Our results show that the measured spectrum gets heavily distorted for large degrees of polarisation or for short charge collection time. We also put these results in context by discussing how they relate to the critical fluence rate and the time of flight of the charge carriers. These results can lead to improved simulation models of CdTe detectors and a better understanding the factors affecting their imaging performance.
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