| 1. |
- 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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| 2. |
- Andersson, Jonathan
(författare)
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Water–fat separation in magnetic resonance imaging and its application in studies of brown adipose tissue
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Virtually all the magnetic resonance imaging (MRI) signal of a human originates from water and fat molecules. By utilizing the property chemical shift the signal can be separated, creating water- and fat-only images. From these images it is possible to calculate quantitative fat fraction (FF) images, where the value of each voxel is equal to the percentage of its signal originating from fat. In papers I and II methods for water–fat signal separation are presented and evaluated.The method in paper I utilizes a graph-cut to separate the signal and was designed to perform well even for a low signal-to-noise ratio (SNR). The method was shown to perform as well as previous methods at high SNRs, and better at low SNRs.The method presented in paper II uses convolutional neural networks to perform the signal separation. The method was shown to perform similarly to a previous method using a graph-cut when provided non-undersampled input data. Furthermore, the method was shown to be able to separate the signal using undersampled data. This may allow for accelerated MRI scans in the future.Brown adipose tissue (BAT) is a thermogenic organ with the main purpose of expending chemical energy to prevent the body temperature from falling too low. Its energy expending capability makes it a potential target for treating overweight/obesity and metabolic dysfunctions, such as type 2 diabetes. The most well-established way of estimating the metabolic potential of BAT is through measuring glucose uptake using 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET) during cooling. This technique exposes subjects to potentially harmful ionizing radiation, and alternative methods are desired. One alternative method is measuring the BAT FF using MRI.In paper III the BAT FF in 7-year olds was shown to be negatively associated with blood serum levels of the bone-specific protein osteocalcin and, after correction for adiposity, thigh muscle volume. This may have implications for how BAT interacts with both bone and muscle tissue.In paper IV the glucose uptake of BAT during cooling of adult humans was measured using 18F-FDG PET. Additionally, their BAT FF was measured using MRI, and their skin temperature during cooling near a major BAT depot was measured using infrared thermography (IRT). It was found that both the BAT FF and the temperature measured using IRT correlated with the BAT glucose uptake, meaning these measurements could be potential alternatives to 18F-FDG PET in future studies of BAT.
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| 3. |
- 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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| 4. |
- 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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| 5. |
- Ebeling Barbier, Charlotte, 1969-
(författare)
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Myocardial Scars on MRI : Their Prevalence and Possible Impact
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Myocardial infarction (MI) causes high morbidity and mortality worldwide and for effective prevention and treatment MIs have to be adequately detected.The existence of clinically unrecognized MIs (UMIs) has been known for the past hundred years, but an ultimate tool for their detection has not yet been found. Using persistent Q waves on electrocardiography as a sign of MI, it has been estimated that UMIs constitute at least ¼ of all MIs and have mortality rates similar to those of recognized MIs (RMIs). These estimates are misleading, however, since persistent Q waves do not necessarily represent MIs.The late enhancement technique in magnetic resonance imaging (LE MRI) has been developed over the past decade and accurately determines myocardial viability. The aim of this research was to investigate the prevalence and impact of UMI and RMI in a population-based sample of 70-year-olds, assessed with MRI.Cardiac function and viability were examined with MRI in 259 randomly selected 70-year-old subjects (127 women, 132 men) participating in a larger population-based study (PIVUS). Information on other parameters of cardiovascular disease was obtained and related to the findings.Three methods for segmentation of the left ventricular mass were used in the first 100 subjects; these differed in accuracy and led to differences in systolic function values. In the subsequent 159 examinations one of the segmentation methods was used.The viability images were assessable in 248 subjects (123 women, 125 men). Among these, the prevalence of UMI, 19.8%, definitely exceeded the expectations and UMIs constituted 4/5 of all MIs. The prevalence of RMI was 4.4%. MRI-detected UMIs differed from RMIs in several respects; they were smaller, frequently located inferolaterally, did not appear to be associated with atherosclerosis, and displayed increased collagen turnover. The pathogenesis of these UMIs remains to be investigated, but our observations suggest that they are caused by ischemia. Subjects with UMI showed increased cardiac morbidity, a decreased ejection fraction and an increased left ventricular mass, indicating an increased cardiovascular risk.It is thus important to detect these UMIs, and this is adequately achieved by LE MRI. However, to decide upon prevention and treatment of these UMIs we need to know more about their pathogenesis and prognosis.
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| 6. |
- Edwards, David, 1971-
(författare)
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Pre-Clinical Evaluation of a Novel Radiotracer for the Diagnosis of DVT and Pulmonary Embolism.
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Deep vein thrombosis (DVT) and pulmonary embolism (PE) are different aspects of a single condition, venous thrombo-embolic disease (VTE), a major cause of morbidity and mortality in the western world. Rapid diagnosis is critical, as timely medical intervention can have a substantial beneficial effect on the mortality rate. Irrespective of its presentation, VTE is a difficult disease to diagnose. Pathologies unrelated to VTE can give rise to a clinical presentation similar to DVT or PE, resulting in a false positive diagnosis. This raises the risk of a patient being treated inappropriately. Therefore, there is a need for an agent that has high specificity and sensitivity for the detection of active blood clots, which are amenable to treatment by anticoagulant and/or thrombolytic therapy. This work describes the pre-clinical efficacy studies performed on one such agent, 99mTc-NC100668. 99mTc-NC100668 is a substrate for factor XIIIa and as a potential physiological, rather than anatomical, marker of VTE it is hoped it will not give rise to the false negative and positive diagnoses that are inherent in the currently available diagnostic techniques, such as the ventilation perfusion (V/Q) scan, multidetector computer tomography or ultrasound. It is reported in this work that 99mTc-NC100668 uptake and retention in blood clot was rapid and maintained over at least a 4 hour period in a rat model of DVT. Anticoagulant and thrombolytic therapies commonly used to treat thrombosis did not seriously impair the ability of 99mTc-NC100668 to detect thrombi. No significant tissue retention, which could interfere with the ability to image thrombi in vivo, was observed. Biodistribution and plasma clot uptake studies showed that 99mTc complex of gly-NC100194, the major metabolite of 99mTc-NC100668, would be unlikely to affect adversely the clinical utility of the test substance. The in vitro uptake of 99mTc-NC100668 into forming plasma clots indicated that retention into human blood clots would be comparable with the observations made in the rat preclinical models. The uptake of 99mTc-NC100668 in vitro and in vivo was much greater than could be accounted for by physical entrapment into the forming blood clots. The reduced uptake of a biologically inactive analogue of 99mTc-NC100668 both in vitro and in vivo indicated that the blood clot uptake and retention of 99mTc-NC100668 was mediated by factor XIIIa. In conclusion, 99mTc-NC100668 might be useful in the detection of thrombo embolism.
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| 7. |
- Ekström, Simon, 1991-
(författare)
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Efficient GPU-based Image Registration : for Detailed Large-Scale Whole-body Analysis
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Imaging has become an important aspect of medicine, enabling visualization of internals in a non-invasive manner. The rapid advancement and adoption of imaging techniques have led to a demand for tools able to take advantage of the information that is produced. Medical image analysis aims to extract relevant information from acquired images to aid diagnostics in healthcare and increase the understanding within medical research. The main subject of this thesis, image registration, is a widely used tool in image analysis that can be employed to find a spatial transformation aligning a set of images. One application, that is described in detail in this thesis, is the use of image registration for large-scale analysis of whole-body images through the utilization of the correspondences defined by the resulting transformations. To produce detailed results, the correspondences, i.e. transformations, need to be of high resolution and the quality of the result has a direct impact on the quality of the analysis. Also, this type of application aims to analyze large cohorts and the value of a registration method is not only weighted by its ability to produce an accurate result but also by its efficiency. This thesis presents two contributions on the subject; a new method for efficient image registration with the ability to produce dense deformable transformations, and the application of the presented method in large-scale analysis of a whole-body dataset acquired using an integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) system. In this thesis, it is shown that efficient and detailed image registration can be performed by employing graph cuts and a heuristic where the optimization is performed on subregions of the image. The performance can be improved further by the efficient utilization of a graphics processing unit (GPU). It is also shown that the method can be employed to produce a model on health based on a PET-MRI dataset which can be utilized to automatically detect pathology in the imaging.
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| 8. |
- 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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| 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. |
- Johansson, Lars, 1966-
(författare)
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The Utility of Ultrasmall Superparamagnetic Iron Oxide Contrast Agents for Cardiovascular Magnetic Resonance Imaging
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this thesis was to investigate the utility of the Ultrasmall Superparamagnetic Iron Oxide Particle (USPIO), NC100150 Injection for assessment of macro- and microvascular morphology and function using magnetic resonance imaging. The feasibility of NC100150 Injection was tested for the following applications: Coronary angiography, Thrombus detection, Cardiac function, Myocardial perfusion, Assessment of myocardial blood volume and water exchange and finally assessment of endothelial integrity of the myocardium.The test method included computer simulations, in vitro, animal and clinical experiments. The computer simulations included propagation of longitudinal magnetization in non-steady state acquisitions. Animal models used were coronary artery stenosis in pigs, thrombus formation in the jugular vein in pigs, normal pig myocardium and transplanted hearts in rats. A human study of patients with suspected coronary artery disease was also performed.The results showed that angiography using an USPIO is less efficient in the coronary arteries than in the peripheral arteries. Direct targeting to thrombus using an USPIO is possible but will be limited by the spatial resolution. An USPIO will enhance gradient echo imaging of cardiac function. T2-weighted myocardial perfusion imaging is feasible as well as assessment of myocardial blood volume and endothelial integrity.Due to physiological limitations and technical development the utility of NC100150 Injection for assessment of the macrovascular morphology is limited.However for the assessment of microvascular function, especially perfusion and permeability, NC100150 Injection may contribute to a successful implementation of these methods.
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