| 1. |
- Eriksson, Olof, 1978-
(författare)
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Imaging Islets of Langerhans by Positron Emission Tomography : Quantification of Beta-Cell Mass in the Native Pancreas and the Islet Graft
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 1 and 2 Diabetes Mellitus are a growing health problem throughout the world. There is an increasing need for methodologies, which are both reliable and non-invasive to measure the amount of insulin-producing tissue (Beta-cell mass, or BCM), as well as rapidly quantify changes in the BCM due to the onset of disease, beta-cell replacement therapy, or other treatments. Positron Emission Tomography (PET) is a non-invasive, quantitative functional imaging technique which can be used to study dynamical or static processes inside the body. In this thesis, we present a study protocol for in vivo imaging of the most common form of beta- cell replacement therapy; islet transplantation. Islets were labeled with the PET tracer, 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG), and administered intra-portally, while the recipient was monitored by PET/CT. The hepatic distribution of the islets was highly heterogeneous, and around 25% (human) or 50% (porcine) of the administered islets could not be found in the liver after completed transplantation, confirming previous reports of considerable cell injury during the procedure leading to low hepatic engraftment. Native BCM in the pancreas can potentially be quantified using a PET tracer with sufficiently high specificity, but the major obstacle is the relative low amounts of insulin producing tissue (only 1-2% of the pancreatic volume). Two tetrabenazine analogues, [18F]FE-(+)-DTBZ and [18F]FE-(+)-DTBZ-d4, are ligands to VMAT2, which is expressed in islet tissue. Both analogues were investigated and characterized as potential BCM imaging agents both in vitro and in vivo. Both tracers exhibited high preferential binding to islet tissue compared to exocrine pancreatic tissue. However, the specificity was not high enough to overcome the obscuring exocrine signal in vivo (7-10% of the signal originating from specific islet tracer uptake). This thesis demonstrates that it is possible to quantitatively assess islet transplantation by PET imaging. In vivo determination of native pancreatic BCM is, in theory, possible with both [18F]FE-(+)-DTBZ and [18F]FE-(+)-DTBZ-d4, but tracer analogues with higher islet specificity is needed for quantification of smaller BCM changes with physiological impact.
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| 2. |
- Lundberg, Christina, 1972-
(författare)
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Screening for Atherosclerosis with Magnetic Resonance Imaging and Ultrasound
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerosis is a major cause of death and disability worldwide. Although traditional risk factors can identify the healthy or severely affected individuals, sudden lethal outcome is still frequent in those suggested as intermediate in risk for cardiovascular events (CVE). Adding imaging to the traditional scoring systems might improve risk stratification.This thesis investigates whether the addition of magnetic resonance imaging (MRI) and ultrasound (US) to traditional risk factors might render atherosclerosis suitable for mass screening, selective screening or screening in research settings.In paper I the carotid arteries were assessed in six different manners (carotid intima media thickness (CIMT) in two different locations, presence of plaque, number of plaques, plaque size and plaque composition) using US. More than 800 Caucasian subjects were assessed at ages 70 and 75, and outcome examined at 80 years of age. Plaques with an area exceeding 10mm2 in the bulb were found to be most closely related to CVE.Paper II established that carotid plaque volume measured with MRI did not correlate with carotid plaque area assessed with US. MRI reached the highest levels of reproducibility of the two methods.Paper III used the previously created total atherosclerotic score (TAS), a scoring system based on whole body magnetic resonance angiography (WBMRA) that assesses global atherosclerosis. TAS was found to predict CVE in 305 PIVUS-subjects at age 70 years during 5 years of follow-up. The risk for CVE was found to be eightfold with TAS>0.In paper IV CIMT was assessed with US at ages 70 and 75 years. CIMT at baseline, but not the change in CIMT over five years, was significantly related to TAS, thus suggesting carotid changes to correlate with atherosclerosis throughout the body.In conclusion, in research settings WBMRA and MRI, as well as US, can be used for screening and following up of atherosclerotic changes, as their predictive values and reproducibility are good. US might be feasible in selective screening but none of these methods are as of now suitable for mass screening.
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| 3. |
- Andersson, Camilla
(författare)
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PET/CT in oncology : Patient experience, image quality and the value of information
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim was to investigate patients’ experiences with a PET/CT examination, satisfaction with care provided in connection to the examination and whether web-based information can improve satisfaction with care and image quality, compared to standard care. An additional aim was to explore how satisfaction with care and image quality is associated with health-related quality of life (HRQoL) and perceived stress. Methods: Study I and IV included patients with known or suspected malignancy scheduled for an 18F-FDG PET/CT examination. Study II included prostate cancer patients with known or suspected bone metastases scheduled for an 18F-fluoride PET/CT examination, and study III included head and neck cancer patients scheduled for an 18F-FDG PET/CT examination in a fixation mask. Study I and II had cross-sectional designs, study III used a phenomenological methodology according to Max van Manen, and study IV was a randomized controlled trial. Results: Study I and II found that many patients did not know before what a PET/CT examination was but were satisfied with care provided by the nursing staff. In study II the image quality was high and there was no difference in image quality between those patients that experienced pain or discomfort during the PET/CT and those that did not. Study III showed that the patient’s lifeworld was changed during the PET/CT examination and the use of coping strategies helped the patient to endure the examination procedure. In study IV the overall satisfaction, satisfaction single-variables and image quality was high in the intervention group and standard care group. There was no statistically significant difference between patients the intervention group and standard care group. However, there was slightly higher number of detected image quality defects in the standard care group. In study I and IV there were some statistically significant correlations between patient satisfaction and HRQoL (p<0.01-0.05). Conclusion: The results of this thesis may be used to improve patient information and care in connection to PET/CT examinations and thereby help optimize PET/CT imaging procedure. However, the results need to be investigated in larger populations.
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| 4. |
- Kero, Tanja
(författare)
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Methodological aspects of quantitative cardiac molecular imaging
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The objective of this research was to facilitate the use of quantitative cardiac molecular imaging by developing and validating methods and applications. More specifically:we determined the optimal tracer kinetic model for analysis of 11C-PIB and evaluated the performance of two simpler measures, retention index (RI) and standardized uptake value (SUV), in the quantification of cardiac 11C-PIB uptake in amyloidosis. An irreversible two-tissue (2Tirr) model best described the 11C-PIB uptake in cardiac amyloidosis. RI and SUV showed high correlation with quantitative results from this kinetic model and also a better discrimination between amyloidosis patients and controls than a 2Tirr model with population averaged metabolite correction. RI and SUV are furthermore more feasible for use in clinical routine and therefore the preferred measure to use in PET diagnosis of cardiac amyloidosis. We also tested the feasibility of a semiautomatic software to analyze RI and visualize cardiac uptake of 11C-PIB in amyloidosis. The RI values were comparable with RI based on manual segmentation, showing significantly higher 11C-PIB RI in amyloidosis patients than in healthy volunteers. A fast and accurate semiautomatic analysis process is thus feasible to use for PET in cardiac amyloidosis instead of the laborious manual analyses that were used so far.Furthermore, we assessed the quantitative accuracy of cardiac perfusion measurements with 15O-water PET in a digital time-of-flight PET-MR scanner. A high correlation and agreement between PET-MR based and PET-CT based MBF was found; cardiac perfusion measurements with 15O-water can therefore be performed accurately with the fully integrated Signa PET-MR scanner. Finally, we assessed the quantitative accuracy of cardiac perfusion measurements using dynamic contrast-enhanced MRI with simultaneous 15O-water PET as reference at rest and during adenosine-induced hyperemia with a fully integrated PET-MR scanner. The correlations between global and regional MRI- and PET-based MBF values were good and the biases were negliable for both global and regional MBF comparisons, but the limits of agreement were wide for both global and regional MBF, with larger variability for high MBF-values indicating that MRI-based quantitative MBF measurement based on widely available acquisition protocols is not yet ready for clinical introduction.
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| 5. |
- von Below, Catrin
(författare)
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PET and MRI of Prostate Cancer
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate cancer (PCa) is the most common non-skin malignancy of men in developed countries. In spite of treatment with curative intent up to 30-40% of patients have disease recurrence after treatment, resulting from any combination of lymphatic, hematogenous, or contiguous local spread.The concept of early detection of PCa offer benefits in terms of reduced mortality, but at the cost of over-diagnosis and overtreatment of indolent disease. This is largely due to the random nature of conventional biopsies, with a risk of missing significant cancer and randomly hitting indolent disease.In the present thesis, diagnostic performance of MRI DWI and 11C Acetate PET/CT lymph node staging of intermediate and high risk PCa, was investigated, and additionally, predictive factors of regional lymph node metastases were evaluated. Further, additional value of targeted biopsies to conventional biopsies, for detection of clinically significant PCa, was investigated.In paper one and two, 53 and 40 patients with predominantly high risk PCa underwent 11C Acetate PET/CT and 3T MRI DWI, respectively, for lymph node staging, before extended pelvic lymph node dissection (ePLND). The sensitivity and specificity for PET/CT was 38% and 96% respectively. The sensitivity and specificity for MRI DWI was 55% and 90% respectively.In paper three, 53 patients with newly diagnosed PCa were included. All patients underwent multi-parametric MRI, followed by two cognitive targeted biopsies. Five more clinically significant cancers were detected by adding targeted biopsies to conventional biopsies.In paper four the value of quantitative and qualitative MRI DWI and 11C Acetate PET/CT parameters, alone and in combination, in predicting regional lymph node metastases were examined. ADCmean in lymph nodes and T-stage on MRI were independent predictors of lymph node metastases in multiple logistic regression analysis.In conclusion the specificity of diffusion weighted MRI and 11C Acetate PET/CT for lymph node staging was high, although the sensitivity was low. Predictive factors of regional lymph node metastases could be retrieved from diffusion weighted MRI and 11C Acetate PET/CT. By combining targeted biopsies with conventional biopsies the detection rate of clinically significant PCa could be increased.
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| 6. |
- Berglund, Johan, 1983-
(författare)
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Separation of Water and Fat Signal in Magnetic Resonance Imaging : Advances in Methods Based on Chemical Shift
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Magnetic resonance imaging (MRI) is one of the most important diagnostic tools of modern healthcare. The signal in medical MRI predominantly originates from water and fat molecules. Separation of the two components into water-only and fat-only images can improve diagnosis, and is the premier non-invasive method for measuring the amount and distribution of fatty tissue. Fat-water imaging (FWI) enables fast fat/water separation by model-based estimation from chemical shift encoded data, such as multi-echo acquisitions. Qualitative FWI is sufficient for visual separation of the components, while quantitative FWI also offers reliable estimates of the fat percentage in each pixel. The major problems of current FWI methods are long acquisition times, long reconstruction times, and reconstruction errors that degrade image quality. In this thesis, existing FWI methods were reviewed, and novel fully automatic methods were developed and evaluated, with a focus on fast 3D image reconstruction. All MRI data was acquired on standard clinical scanners. A triple-echo qualitative FWI method was developed for the specific application of 3D whole-body imaging. The method was compared with two reference methods, and demonstrated superior image quality when evaluated in 39 volunteers. The problem of qualitative FWI by dual-echo data with unconstrained echo times was solved, allowing faster and more flexible image acquisition than conventional FWI. Feasibility of the method was demonstrated in three volunteers and the noise performance was evaluated. Further, a quantitative multi-echo FWI method was developed. The signal separation was based on discrete whole-image optimization. Fast 3D image reconstruction with few reconstruction errors was demonstrated by abdominal imaging of ten volunteers. Lastly, a method was proposed for quantitative mapping of average fatty acid chain length and degree of saturation. The method was validated by imaging different oils, using gas-liquid chromatography (GLC) as the reference. The degree of saturation agreed well with GLC, and feasibility of the method was demonstrated in the thigh of a volunteer. The developed methods have applications in clinical settings, and are already being used in several research projects, including studies of obesity, dietary intervention, and the metabolic syndrome.
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| 7. |
- Breznik, Eva
(författare)
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Image Processing and Analysis Methods for Biomedical Applications
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With new technologies and developments medical images can be acquired more quickly and at a larger scale than ever before. However, increased amount of data induces an overhead in the human labour needed for its inspection and analysis. To support clinicians in decision making and enable swifter examinations, computerized methods can be utilized to automate the more time-consuming tasks. For such use, methods need be highly accurate, fast, reliable and interpretable. In this thesis we develop and improve methods for image segmentation, retrieval and statistical analysis, with applications in imaging-based diagnostic pipelines. Individual objects often need to first be extracted/segmented from the image before they can be analysed further. We propose methodological improvements for deep learning-based segmentation methods using distance maps, with the focus on fully-supervised 3D patch-based training and training on 2D slices under point supervision. We show that using a directly interpretable distance prior helps to improve segmentation accuracy and training stability.For histological data in particular, we propose and extensively evaluate a contrastive learning and bag of words-based pipeline for cross-modal image retrieval. The method is able to recover correct matches from the database across modalities and small transformations with improved accuracy compared to the competitors. In addition, we examine a number of methods for multiplicity correction on statistical analyses of correlation using medical images. Evaluation strategies are discussed and anatomy-observing extensions to the methods are developed as a way of directly decreasing the multiplicity issue in an interpretable manner, providing improvements in error control. The methods presented in this thesis were developed with clinical applications in mind and provide a strong base for further developments and future use in medical practice.
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| 8. |
- Carlbom, Lina
(författare)
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Positron Emission Tomography and Magnetic Resonance Techniques in Diabetes
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In order to further advance the field of diabetes research there is a great need for establishing validated non-invasive quantitative techniques to study the pancreas and other tissues of importance for blood glucose regulation. The general aim of this thesis was to explore magnetic resonance techniques and positron emission tomography as such tools.In paper I pancreatic perfusion under basal conditions and in response to glucose in nondiabetic and type 1 diabetic individuals was studied with [15O]H2O PET/CT. Individuals with type 1 diabetes were found to have reduced basal pancreatic perfusion and a severely impaired pancreatic and splanchnic perfusion response to intravenous glucose stimulation.In paper II four groups of subjects at different stages of type 2 diabetes development and a control group of individuals without diabetes were examined with PET/CT and MRI. The [11C]5-HTP uptake in pancreas was hypothesized to correlate with remaining functional capacity of the β-cells. The progressive loss of β-cell function indicated by metabolic testing was not mirrored by a decrease in [11C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased β-cell function, indicating that β-cell dysfunction or dedifferentiation, and not necessarily endocrine cell loss, constitutes a major cause of β-cell failure in type 2 diabetes.In paper III the feasibility of using ex-vivo MR spectroscopy for assessment of viability of human pancreas grafts prior to transplantation was studied. It was found that 31P-MRS may provide quantitative parameters for evaluating graft viability ex vivo, and is a promising tool for objective non-invasive assessment of the quality of human pancreas grafts.In paper IV the Imiomics method for automatic image analysis was validated in whole-body [18F]-FDG PET/MR images in subjects with varying degree of insulin resistance. Imiomics was found to provide association screening and timesaving analysis of whole-body data and detected differences in glucose uptake and tissue composition between subjects on voxel-level. However, it did not show complete correlation with traditional volume of interest based tissue analysis in a small cohort.
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| 9. |
- Eriksson, Rolf, 1979-
(författare)
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The Utility of Manganese for Magnetic Resonance Imaging of Transient Myocardial Ischemia
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In order to improve the diagnosis of coronary artery disease, better methods for detection of myocardial perfusion defects would be useful. One of the methods used for myocardial perfusion evaluation today is magnetic resonance imaging. This method could be improved if a contrast agent that induced long-lasting contrast enhancement in the myocardium could be developed. The paramagnetic manganese(II) ion has promising properties for meeting this need, since it enters cardiomyocytes through voltage-gated calcium channels and remains inside the cells for a long time after an intravenous injection. If these properties can be utilized, manganese-enhanced MRI has potential for detecting transient periods of ischemia in a manner similar to the conventional SPECT stress test.To investigate the contrast-enhancing properties of the manganese(II) ion, a series of experiments was performed in pigs, using a manganese salt (MnCl2) and two manganese-based chelates (MnDPDP and MnHPTA) and measuring the longitudinal relaxation rates before and after contrast agent administration. This was done in normal pig myocardium at rest and during dobutamine-induced stress with several different doses of contrast agent, and in a model for coronary artery stenosis using MnCl2 administered during dobutamine stress to determine whether transient ischemia could be detected with this contrast agent.The results of these experiments showed that of the three contrast agents, MnCl2 induces the greatest increase in ΔR1, followed by MnHPTA. Using MnCl2 it was possible to produce images on which transient myocardial ischemia was visible, but only during the first 30 minutes after contrast agent injection.The stenosis model is still far from the clinical situation and several complications, including the potential toxicity of the manganese(II) ion, remain to be overcome. However, the results from this model are promising for the future development of manganese- enhanced magnetic resonance imaging of transient myocardial ischemia.
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| 10. |
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