| 1. |
- Strandberg, Johan, 1981-
(författare)
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Non-parametric methods for functional data
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis we develop and study non-parametric methods within three major areas of functional data analysis: testing, clustering and prediction. The thesis consists of an introduction to the field, a presentation and discussion of the three areas, and six papers.In Paper I, we develop a procedure for testing for group differences in functional data. In case of significant group differences, the test procedure identifies which of the groups that significantly differ, and also the parts of the domain they do so, while controlling the type I error of falsely rejecting the null hypothesis. In Paper II, the methodology introduced in Paper I is applied to knee kinematic curves from a one-leg hop for distance to test for differences within and between three groups of individuals (with and without knee deficits). It was found that two of the groups differed in their knee kinematics. We also found that the individual kinematic patterns differed between the two legs in one of the groups. In Paper III, we test for group differences in three groups with respect to joint kinematics from a vertical one-leg hop using a novel method that allows accounting for multiple joints at the same time. The aim of Paper III, as one of few within the field of biomechanics, is to illustrate how different choices prior to the analysis can result in different contrasting conclusions. Specifically, we show how the conclusions depend on the choice of type of movement curve, the choice of leg for between-group comparisons and the included joints.In Paper IV, we present a new non-parametric clustering method for dependent functional data, the double clustering bagging Voronoi method. The objective of the method is to identify latent group structures that slowly vary over domain and give rise to different frequency patterns of functional data object types. The method uses a bagging strategy based on random Voronoi tessellations in which local representatives are formed and clustered. Combined with the clustering method, we also propose a multiresolution approach which allows identification of latent structures at different scales. A simulated dataset is used to illustrate the method's potential in finding stable clusters at different scales. The method is also applied to varved lake sediment data with the aim of reconstructing the climate over the past 6000 years, at different resolutions. In Paper V, we expand and modify the bagging strategy used in Paper IV, by considering different methods of generating the tessellations and clustering the local representatives of the tessellations. We propose new methods for clustering dependent categorical data (e.g., labelled functional data) along a one-dimensional domain, which we also compare in a simulation study. In Paper VI, two kriging approaches to predict spatial functional processes are compared, namely functional kriging and spatio-temporal kriging. A simulation study is conducted to compare their prediction performance and computational times. The overall results show that prediction performance is about the same for stationary spatio-temporal processes while functional kriging works better for non-stationary spatio-temporal processes. Furthermore, the computational time for (ordinary) kriging for functional data, was considerably lower than spatio-temporal kriging. Conditions are also formulated under which it is proved that the two functional kriging methods: ordinary kriging for functional data and pointwise functional kriging coincide.
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| 2. |
- Andrean, Stefio Yosse, 1991-
(författare)
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Search for New Scalar Particles with ATLAS
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Large Hadron Collider (LHC) is currently the most powerful particle accelerator ever built. It accelerates protons and collides them at the center of mass energy of √s = 13 TeV. At one of the collision points of LHC, a general-purpose particle detector — ATLAS — is installed to measure the outgoing particles produced in the collisions allowing the study of interactions between the elementary particles. The work presented in this thesis uses the collisions data produced by LHC and the data collected by ATLAS during the period of 2015-2018 which amounts to the integrated luminosity of 139 fb-1.This thesis focuses on searches of spin-0 particles in two areas of Beyond Standard Model physics: supersymmetry and extended Higgs sector. Supersymmetry offers a solution to the hierarchy problem by introducing partners to every Standard Model particle. Stop — the superpartner of the top quark — is particularly interesting due to its ability to cancel the dominant top contribution in the Higgs boson mass loop correction, and therefore becomes the target of a search in this thesis. Many Beyond Standard Model scenarios extend the Higgs sector for they are motivated by neutrino oscillations, dark matter, and baryogenesis. One of the consequences of these scenarios is the prediction of extra Higgs-like scalar particles which may decay into the 125 GeV Higgs boson. This is the signature targeted by the second ATLAS data analysis documented in this thesis.The thesis also includes a performance study of the Tile Calorimeter. The Tile Calorimeter is part of the ATLAS calorimeter system whose main task is to measure the energy of hadrons. The study is conducted on the Tile Calorimeter using muons from W boson decay originating from proton-proton collisions. Each calorimeter cell response is measured in data and compared with detector simulation to verify that the energy scale in simulation matches that in the real detector.
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| 3. |
- Pasuwan, Patrawan, 1990-
(författare)
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Searches for dark matter in association with top quarks with the ATLAS experiment
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents a search for dark matter with the ATLAS experiment using 139 fb−1 of pp collision data at √s = 13 TeV delivered by the LHC from 2015 to 2018. The search targets a simplified model where a spin-0 scalar or pseudoscalar mediator particle, decaying to a pair of dark matter particles, is produced in association with a pair of top quarks. The final state of interest includes one charged lepton, multiple jets and missing transverse momentum. No excess over the Standard Model background is observed and new exclusion limits at 95% confidence level are placed on the mediator mass. Mediator masses up to 200 GeV are excluded for a dark matter mass of 1 GeV and a coupling strength of one. The one-lepton analysis is statistically combined with those targeting final states with zero or two leptons. The combined results extend the exclusion limits for mediator masses up to 370 GeV. These results are also used to set an upper limit on the Higgs boson branching ratio into invisible particles of 0.40 at 95% confidence level. Luminosity is a key measure of the LHC performance which relates the number of events of a physics process to its cross-section. This thesis presents systematic studies of the track-counting algorithm which is used to measure the luminosity in ATLAS.
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| 4. |
- Strandberg, Sara, 1976-
(författare)
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11C-Acetate-PET/CT in Primary Staging of High-Risk Prostate Cancer
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate cancer (PC) is the second most common cancer in men worldwide, affecting ~12%. Although most are clinically insignificant low-risk cancers, the more aggressive high-risk cancers require correct staging, prior to curative radiotherapy or surgery. Standard staging procedures and tools include clinical examination, estimated nomogram risk of pelvic lymph node (LN) metastases, and bone scintigraphy (BS). Additional staging information can be obtained with magnetic resonance imaging (MRI), computed tomography (CT) and positron-emission tomography/computed tomography (PET/CT). PET/CT can provide information on both functional and morphological changes.The aims of the present thesis were to investigate the diagnostic and prognostic value of 11C-acetate (ACE)-PET/CT in high-risk PC, and to optimize the ACE-PET protocol. In study I and II, higher detection rates of LN metastases and bone metastases were found with ACE-PET/CT, than with standard methods nomogram risk and BS. The higher ACE uptake in the prostate (prostate lipogenic tumor burden), the higher the risk of suspected LN metastases (N+ disease) on PET/CT. ACE-PET/CT findings correlated better than BS with follow-up data, and influenced therapy in 11-43%. In study III, PET reconstruction algorithm with resolution recovery showed more accurate functional tumor volumes compared to CT, and higher measurements of lipogenic activity, than reconstruction algorithm without resolution recovery. Study IV was part of an interventional radiotherapy study (PARAPLY) on high-risk PC, with addition of image-guided simultaneous integrated boost to delineated prostate tumors and pelvic LN metastases reported in ACE-PET/CT and MRI. Comparative analyses of clinical risk parameters and baseline ACE-PET/CT parameters showed significant associations between nomogram risk and prostate lipogenic tumor burden, between N+ disease on PET/CT and prostate lipogenic tumor burden, but surprisingly not between nomogram risk and N+ disease on PET/CT. PET with resolution recovery was superior in detection of N+ disease.In conclusion, ACE-PET/CT showed a higher detection rate of suspected metastases compared to standard methods clinical nomogram and BS, in high-risk PC. PET reconstruction with resolution recovery seems to improve the diagnostic added value of ACE-PET/CT. Prostate lipogenic tumor burden could serve as a predictor of N+ disease. The prognostic value of ACE-PET/CT remains to be investigated in future studies.
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| 5. |
- Abulaiti, Yiming, 1982-
(författare)
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Search for Pair-Produced Supersymmetric Top Quark Partners with the ATLAS Experiment
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Searches for the supersymmetric partner of the top quark (stop) are motivated by natural supersymmetry, where the stop has to be light to cancel the large radiative corrections to the Higgs boson mass. This thesis presents three different searches for the stop at √s = 8 TeV and √s = 13 TeV using data from the ATLAS experiment at CERN’s Large Hadron Collider. The thesis also includes a study of the primary vertex reconstruction performance in data and simulation at √s = 7 TeV using tt and Z events. All stop searches presented are carried out in final states with a single lepton, four or more jets and large missing transverse energy. A search for direct stop pair production is conducted with 20.3 fb−1 of data at a center-of-mass energy of √s = 8 TeV. Several stop decay scenarios are considered, including those to a top quark and the lightest neutralino and to a bottom quark and the lightest chargino. The sensitivity of the analysis is also studied in the context of various phenomenological MSSM models in which more complex decay scenarios can be present. Two different analyses are carried out at √s = 13 TeV. The first one is a search for both gluino-mediated and direct stop pair production with 3.2 fb−1 of data while the second one is a search for direct stop pair production with 13.2 fb−1 of data in the decay scenario to a bottom quark and the lightest chargino. The results of the analyses show no significant excess over the Standard Model predictions in the observed data. Consequently, exclusion limits are set at 95% CL on the masses of the stop and the lightest neutralino.
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| 6. |
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| 7. |
- Björeland, Ulrika, et al.
(författare)
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Impact of neoadjuvant androgen deprivation therapy on magnetic resonance imaging features in prostate cancer before radiotherapy
- 2021
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Ingår i: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 17, s. 117-123
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: In locally advanced prostate cancer (PC), androgen deprivation therapy (ADT) in combination with whole prostate radiotherapy (RT) is the standard treatment. ADT affects the prostate as well as the tumour on multiparametric magnetic resonance imaging (MRI) with decreased PC conspicuity and impaired localisation of the prostate lesion. Image texture analysis has been suggested to be of aid in separating tumour from normal tissue. The aim of the study was to investigate the impact of ADT on baseline defined MRI features in prostate cancer with the goal to investigate if it might be of use in radiotherapy planning.Materials and methods: Fifty PC patients were included. Multiparametric MRI was performed before, and three months after ADT. At baseline, a tumour volume was delineated on apparent diffusion coefficient (ADC) maps with suspected tumour content and a reference volume in normal prostatic tissue. These volumes were transferred to MRIs after ADT and were analysed with first-order -and invariant Haralick -features.Results: At baseline, the median value and several of the invariant Haralick features of ADC, showed a significant difference between tumour and reference volumes. After ADT, only ADC median value could significantly differentiate the two volumes.Conclusions: Invariant Haralick -features could not distinguish between baseline MRI defined PC and normal tissue after ADT. First-order median value remained significantly different in tumour and reference volumes after ADT, but the difference was less pronounced than before ADT.
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| 8. |
- Carney, Rebecca, 1990-
(författare)
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Silicon Tracking and a Search for Long-lived Particles
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The ATLAS Detector, below the surface of the Swiss-French border, measures the remnants of high-energy proton-proton collisions, accelerated by the Large Hadron Collider (LHC) at CERN. Recently the LHC paused operations, having delivered an integrated luminosity corresponding to 150 fb−1 of data at a centre-of-mass energy of 13 TeV. This thesis describes a search for physics beyond the Standard Model using that dataset as well as the charged particle tracking detector technology that renders it possible. The analysis searches for long-lived, massive particles identified by a characteristic decay displaced from the interaction point and produced in association with high momentum jets.Searching for rare processes requires sifting through a large amount of data, which stresses the ATLAS computing infrastructure. As such, measures are taken to reduce unnecessary computations and supplement our existing resources with, for example, inherently parallel computing architectures. Early adoption of these new architectures is necessary to understand the feasibility of their potential integration, including porting existing algorithms. A popular algorithm used in track reconstruction, the Kalman filter, has been implemented in a neuromorphic architecture: IBM’s TrueNorth. The limits of using such an architecture for tracking, as well as how its performance compares to a non-spiking Kalman filter implementation, are explored in this thesis.In 2026 the LHC will enter a High Luminosity phase (HL-LHC), increasing the instantaneous luminosity by a factor of five and delivering 4000 fb-1 within twelve years. This will impose significant technical challenges on all aspects of the ATLAS detector, resulting in the entire ATLAS Inner Detector being replaced by an all-silicon tracker. ITk (the new “Inner TracKer”) will be comprised of Strip and Pixel detectors. The layout of the Pixel and Strip detectors was optimised for the upgrade to extend their forward coverage. To cope with the increased number of hits per chip per event and explore novel techniques for dealing with the conditions in HL-LHC, an inter-experiment collaboration, RD53, was formed, tasked with producing a front-end readout chip used in Pixel detectors. This thesis will briefly outline the author’s contribution to both of these projects.ITk silicon sensors will undergo significant damage over their lifetime due to non-ionising energy loss (NIEL). This damage must be incorporated into the detector simulation both to predict the detector performance and to understand the effects of radiation damage on data taking. The implementation of NIEL radiation damage in the ATLAS simulation framework is discussed in this thesis.
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| 9. |
- Nilsson, Erik, et al.
(författare)
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The grade of individual prostate cancer lesions predicted by magnetic resonance imaging and positron emission tomography
- 2023
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Ingår i: Communications Medicine. - : Springer Nature. - 2730-664X. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET) are widely used for the management of prostate cancer (PCa). However, how these modalities complement each other in PCa risk stratification is still largely unknown. We aim to provide insights into the potential of mpMRI and PET for PCa risk stratification.Methods: We analyzed data from 55 consecutive patients with elevated prostate-specific antigen and biopsy-proven PCa enrolled in a prospective study between December 2016 and December 2019. [68Ga]PSMA-11 PET (PSMA-PET), [11C]Acetate PET (Acetate-PET) and mpMRI were co-registered with whole-mount histopathology. Lower- and higher-grade lesions were defined by International Society of Urological Pathology (ISUP) grade groups (IGG). We used PET and mpMRI data to differentiate between grades in two cases: IGG 3 vs. IGG 2 (case 1) and IGG ≥ 3 vs. IGG ≤ 2 (case 2). The performance was evaluated by receiver operating characteristic (ROC) analysis.Results: We find that the maximum standardized uptake value (SUVmax) for PSMA-PET achieves the highest area under the ROC curve (AUC), with AUCs of 0.72 (case 1) and 0.79 (case 2). Combining the volume transfer constant, apparent diffusion coefficient and T2-weighted images (each normalized to non-malignant prostatic tissue) results in AUCs of 0.70 (case 1) and 0.70 (case 2). Adding PSMA-SUVmax increases the AUCs by 0.09 (p < 0.01) and 0.12 (p < 0.01), respectively.Conclusions: By co-registering whole-mount histopathology and in-vivo imaging we show that mpMRI and PET can distinguish between lower- and higher-grade prostate cancer, using partially discriminative cut-off values.
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| 10. |
- Pereira Sánchez, Laura, 1995-
(författare)
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The Beauty in Broken Symmetries : b-jet identification and searches for Supersymmetry, Dark Matter and multi-Higgs boson production with the ATLAS experiment
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Large Hadron Collider is the largest and most powerful accelerator in the world. Proton bunches are accelerated to 6.5 TeV inside the LHC ring in opposite directions and are then collided at four different points around the ring with an energy of 13 TeV. The ATLAS detector is a general purpose particle physics detector built around one of the collision points and is used to study the products of the high energy proton-proton collisions. The identification of jets containing b-hadrons (b-jets) is an important part of many physics analyses, including those presented in this thesis. The calibration of the b-jet identification algorithms is performed with data. The first paper of this thesis describes the method to calibrate the probability of a light jet to be mistakenly identified as a b-jet. The second paper presents a search for new phenomena in events with top quark pairs and large missing transverse energy. No evidence for physics beyond the Standard Model is found and the analysis is instead used to exclude various extensions of the Standard Model. The third paper describes the search for Higgs boson pair production in a final state with two photons and two b-jets and the fourth paper a novel Effective Field Theory interpretation of this search. Finally, a search for models with beyond the Standard Model Higgs bosons, X and S, in a final state with two photons and two b-jets is presented. The signal targeted by this search is the resonant production of an X boson that decays to an S and the Standard Model Higgs boson H. This search is under development and the results have not yet been published. All papers included in this thesis use data recorded by the ATLAS detector between 2015 and 2018, during the Run 2 of the Large Hadron Collider.
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| 11. |
- Sandgren, Kristina, et al.
(författare)
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Histopathology-validated lesion detection rates of clinically significant prostate cancer with mpMRI, [68Ga]PSMA-11-PET and [11C]Acetate-PET
- 2023
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Ingår i: Nuclear medicine communications. - : Lippincott Williams & Wilkins. - 0143-3636 .- 1473-5628. ; 44:11, s. 997-1004
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Tidskriftsartikel (refereegranskat)abstract
- Objective: PET/CT and multiparametric MRI (mpMRI) are important diagnostic tools in clinically significant prostate cancer (csPC). The aim of this study was to compare csPC detection rates with [68Ga]PSMA-11-PET (PSMA)-PET, [11C] Acetate (ACE)-PET, and mpMRI with histopathology as reference, to identify the most suitable imaging modalities for subsequent hybrid imaging. An additional aim was to compare inter-reader variability to assess reproducibility.Methods: During 2016–2019, all study participants were examined with PSMA-PET/mpMRI and ACE-PET/CT prior to radical prostatectomy. PSMA-PET, ACE-PET and mpMRI were evaluated separately by two observers, and were compared with histopathology-defined csPC. Statistical analyses included two-sided McNemar test and index of specific agreement.Results: Fifty-five study participants were included, with 130 histopathological intraprostatic lesions >0.05 cc. Of these, 32% (42/130) were classified as csPC with ISUP grade ≥2 and volume >0.5 cc. PSMA-PET and mpMRI showed no difference in performance (P = 0.48), with mean csPC detection rate of 70% (29.5/42) and 74% (31/42), respectively, while with ACE-PET the mean csPC detection rate was 37% (15.5/42). Interobserver agreement was higher with PSMA-PET compared to mpMRI [79% (26/33) vs 67% (24/38)]. Including all detected lesions from each pair of observers, the detection rate increased to 90% (38/42) with mpMRI, and 79% (33/42) with PSMA-PET.Conclusion: PSMA-PET and mpMRI showed high csPC detection rates and superior performance compared to ACE-PET. The interobserver agreement indicates higher reproducibility with PSMA-PET. The combined result of all observers in both PSMA-PET and mpMRI showed the highest detection rate, suggesting an added value of a hybrid imaging approach.
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| 12. |
- Sandgren, Kristina, et al.
(författare)
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Registration of histopathology to magnetic resonance imaging of prostate cancer
- 2021
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Ingår i: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 18, s. 19-25
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The diagnostic accuracy of new imaging techniques requires validation, preferably by histopathological verification. The aim of this study was to develop and present a registration procedure between histopathology and in-vivo magnetic resonance imaging (MRI) of the prostate, to estimate its uncertainty and to evaluate the benefit of adding a contour-correcting registration.Materials and methods: For twenty-five prostate cancer patients, planned for radical prostatectomy, a 3D-printed prostate mold based on in-vivo MRI was created and an ex-vivo MRI of the specimen, placed inside the mold, was performed. Each histopathology slice was registered to its corresponding ex-vivo MRI slice using a 2D-affine registration. The ex-vivo MRI was rigidly registered to the in-vivo MRI and the resulting transform was applied to the histopathology stack. A 2D deformable registration was used to correct for specimen distortion concerning the specimen's fit inside the mold. We estimated the spatial uncertainty by comparing positions of landmarks in the in-vivo MRI and the corresponding registered histopathology stack.Results: Eighty-four landmarks were identified, located in the urethra (62%), prostatic cysts (33%), and the ejaculatory ducts (5%). The median number of landmarks was 3 per patient. We showed a median in-plane error of 1.8 mm before and 1.7 mm after the contour-correcting deformable registration. In patients with extraprostatic margins, the median in-plane error improved from 2.1 mm to 1.8 mm after the contour-correcting deformable registration.Conclusions: Our registration procedure accurately registers histopathology to in-vivo MRI, with low uncertainty. The contour-correcting registration was beneficial in patients with extraprostatic surgical margins.
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| 13. |
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| 14. |
- Wallängen, Veronica, 1986-
(författare)
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Performance Improvements for Particle Tracking Detectors in Extreme Rate and Radiation Environments
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In order to increase its discovery potential, the Large Hadron Collider (LHC) at CERN is being transformed into a higher luminosity machine expected to be operational around 2026. The number of particle collisions will increase by a factor of 10 beyond the current design value, which means that the detectors installed around the LHC are facing various new challenges. The most demanding challenges include handling the enormous data quantities that will be transferred from the front-end readout modules at significantly higher rates than previously, as well as the radiation effects that arise as a consequence of the intense particle flow and that cause damage to sensor elements and electronics.At the ATLAS experiment, a multipurpose detector operating at the LHC, the impact of the luminosity increase is especially severe for the silicon pixel tracking detector, being the central subsystem located closest to the particle interaction point and therefore exposed to the highest radiation dose and hit density. The extreme radiation doses that the pixel modules will be subject to will cause deformation of the sensor material structure and thus loss of the signals, which after subsequent digitization by the pixel readout chip must be transferred over relatively long distances through a low-mass data link, causing further signal distortion.The work presented here addresses both major challenges described and outlines solutions for the upcoming upgrade of the ATLAS pixel detector system with regards to these. Firstly, it is demonstrated how improved accuracy of detector simulations and reconstruction of particle trajectories through the detector can be achieved as higher particle fluences are approached, by modeling radiation damage effects that occur in the pixel sensors. Secondly, it is shown how a receiver integrated circuit utilizing an industry standard technique novel within high-energy physics applications has been designed as an integral part of a high-speed transmission link to efficiently restore the signal quality in order to achieve adequate data readout rates.
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| 15. |
- Zarei, Maryam, et al.
(författare)
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Accuracy of gross tumour volume delineation with [68Ga]-PSMA-PET compared to histopathology for high-risk prostate cancer
- 2024
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Ingår i: Acta Oncologica. - : MJS Publishing, Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 503-510
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation could translate into reduced tumour control and potentially increase the side effects. The purpose of this study is to compare PET-based delineation methods with histopathology.MATERIALS AND METHODS: The study population consisted of 15 patients with confirmed high-risk PC intended for prostatectomy. [68Ga]-PSMA-PET/MR was performed prior to surgery. Prostate lesions identified in histopathology were transferred to the in vivo [68Ga]-PSMA-PET/MR coordinate system. Four radiation oncologists manually delineated intraprostatic lesions based on PET data. Various semi-automatic segmentation methods were employed, including absolute and relative thresholds, adaptive threshold, and multi-level Otsu threshold.RESULTS: The gross tumour volumes (GTVs) delineated by the oncologists showed a moderate level of interobserver agreement with Dice similarity coefficient (DSC) of 0.68. In comparison with histopathology, manual delineations exhibited the highest median DSC and the lowest false discovery rate (FDR) among all approaches. Among semi-automatic approaches, GTVs generated using standardized uptake value (SUV) thresholds above 4 (SUV > 4) demonstrated the highest median DSC (0.41), with 0.51 median lesion coverage ratio, FDR of 0.66 and the 95th percentile of the Hausdorff distance (HD95%) of 8.22 mm.INTERPRETATION: Manual delineations showed a moderate level of interobserver agreement. Compared to histopathology, manual delineations and SUV > 4 exhibited the highest DSC and the lowest HD95% values. The methods that resulted in a high lesion coverage were associated with a large overestimation of the size of the lesions.
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