Quantum Tomography with Phase Space Measurements

This thesis addresses the use of covariant phase space observables in quantum tomography. Necessary and sufficient conditions for the informational completeness of covariant phase space observables are proved, and some state reconstruction formulae are derived. Different measurement schemes for measuring phase space observables are considered. Special emphasis is given to the quantum optical eight-port homodyne detection scheme and, in particular, on the effect of non-unit detector efficiencies on the measured observable. It is shown that the informational completeness of the observable does not depend on the efficiencies. As a related problem, the possibility of reconstructing the position and momentum distributions from the marginal statistics of a phase space observable is considered. It is shown that informational completeness for the phase space observable is neither necessary nor sufficient for this procedure. Two methods for determining the distributions from the marginal statistics are presented. Finally, two alternative methods for determining the state are considered. Some of their shortcomings when compared to the phase space method are discussed.

Imaging of Tumour Microenvironment for the Planning of Oncological Therapies Using Positron Emission Tomography

Tumour cells differ from normal tissue cells in several important ways. These differences, like for example changed energy metabolism, result in altered microenvironment of malignant tumours. Non-invasive imaging of tumour microenvironment has been at the centre of intense research recently due to the important role that this changed environement plays in the development of malignant tumours and due to the role it plays in the treatment of these tumours. In this respect, perhaps the most important characteristics of the tumour microenvironment from this point of view are the lack of oxygen or hypoxia and changes in blood flow (BF). The purpose of this thesis was to investigate the processes of energy metabolism, BF and oxygenation in head and neck cancer and pancreatic tumours and to explore the possibilities of improving the methods for their quantification using positron emission tomography (PET). To this end [18F]EF5, a new PET tracer for detection of tumour hypoxia was investigated. Favourable uptake properties of the tracer were observed. In addition, it was established that the uptake of this tracer does not correlate with the uptake of existing tracers for the imaging of energy metabolism and BF, so the information about the presence of tissue hypoxia cannot therefore be obtained using tracers such as [18F]FDG or [15O]H2O. These results were complemented by the results of the follow-up study in which it was shown that the uptake of [18F]EF5 in head and neck tumours prior to treatment is also associated with the overall survival of the patients, indicating that tumour hypoxia is a negative prognostic factor and might be associated with therapeutic resistance. The influences of energy metabolism and BF on the survival of patients with pancreatic cancer were investigated in the second study. The results indicate that the best predictor of survival of patients with pancreatic cancer is the relationship between energy metabolism and BF. These results suggest that the cells with high metabolic activity in a hypoperfused tissue have the most aggressive phenotype.

Differentiation of Metabolically Distinct Areas within Head and Neck Region using Dynamic 18F-FDG Positron Emission Tomography Imaging

Positron Emission Tomography (PET) using ¹⁸F-FDG is playing a vital role in the diagnosis and treatment planning of cancer. However, the most widely used radiotracer, ¹⁸F-FDG, is not specific for tumours and can also accumulate in inflammatory lesions as well as normal physiologically active tissues making diagnosis and treatment planning complicated for the physicians. Malignant, inflammatory and normal tissues are known to have different pathways for glucose metabolism which could possibly be evident from different characteristics of the time activity curves from a dynamic PET acquisition protocol. Therefore, we aimed to develop new image analysis methods, for PET scans of the head and neck region, which could differentiate between inflammation, tumour and normal tissues using this functional information within these radiotracer uptake areas. We developed different dynamic features from the time activity curves of voxels in these areas and compared them with the widely used static parameter, SUV, using Gaussian Mixture Model algorithm as well as K-means algorithm in order to assess their effectiveness in discriminating metabolically different areas. Moreover, we also correlated dynamic features with other clinical metrics obtained independently of PET imaging. The results show that some of the developed features can prove to be useful in differentiating tumour tissues from inflammatory regions and some dynamic features also provide positive correlations with clinical metrics. If these proposed methods are further explored then they can prove to be useful in reducing false positive tumour detections and developing real world applications for tumour diagnosis and contouring.

Micro Data Repositories: Increasing the Value of Research on the Web

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Translational models of coronary artery disease, myocardial infarction and heart failure. Development, validation and in vivo imaging studies using positron emission tomography

Coronary artery disease is an atherosclerotic disease, which leads to narrowing of coronary arteries, deteriorated myocardial blood flow and myocardial ischaemia. In acute myocardial infarction, a prolonged period of myocardial ischaemia leads to myocardial necrosis. Necrotic myocardium is replaced with scar tissue. Myocardial infarction results in various changes in cardiac structure and function over time that results in “adverse remodelling”. This remodelling may result in a progressive worsening of cardiac function and development of chronic heart failure. In this thesis, we developed and validated three different large animal models of coronary artery disease, myocardial ischaemia and infarction for translational studies. In the first study the coronary artery disease model had both induced diabetes and hypercholesterolemia. In the second study myocardial ischaemia and infarction were caused by a surgical method and in the third study by catheterisation. For model characterisation, we used non-invasive positron emission tomography (PET) methods for measurement of myocardial perfusion, oxidative metabolism and glucose utilisation. Additionally, cardiac function was measured by echocardiography and computed tomography. To study the metabolic changes that occur during atherosclerosis, a hypercholesterolemic and diabetic model was used with [18F] fluorodeoxyglucose ([18F]FDG) PET-imaging technology. Coronary occlusion models were used to evaluate metabolic and structural changes in the heart and the cardioprotective effects of levosimendan during post-infarction cardiac remodelling. Large animal models were used in testing of novel radiopharmaceuticals for myocardial perfusion imaging. In the coronary artery disease model, we observed atherosclerotic lesions that were associated with focally increased [18F]FDG uptake. In heart failure models, chronic myocardial infarction led to the worsening of systolic function, cardiac remodelling and decreased efficiency of cardiac pumping function. Levosimendan therapy reduced post-infarction myocardial infarct size and improved cardiac function. The novel 68Ga-labeled radiopharmaceuticals tested in this study were not successful for the determination of myocardial blood flow. In conclusion, diabetes and hypercholesterolemia lead to the development of early phase atherosclerotic lesions. Coronary artery occlusion produced considerable myocardial ischaemia and later infarction following myocardial remodelling. The experimental models evaluated in these studies will enable further studies concerning disease mechanisms, new radiopharmaceuticals and interventions in coronary artery disease and heart failure.

Vascular Healing after Coronary Stenting Evaluated by Optical Coherence Tomography

Optical coherence tomography (OCT) is a novel intracoronary imaging application for the assessment of native lesions and coronary stents. The purpose of this thesis was to evaluate the safety and feasibility of frequency-domain OCT (FD-OCT) based on experiences of the Satakunta Central Hospital (I). Early vascular healing was evaluated after implantation of endothelial progenitor cell capturing (II) and bio-active titanium-nitride-oxide coated stents (III) in two studies, each with 20 patients. Vascular healing was also compared after implantation of bio-active and everolimus-eluting stents on 28 patients after 9-month follow-up (IV). Long-term vascular healing of bio-active and paclitaxel-eluting stents was assessed in the last study with 18 patients (V). The results indicate that FD-OCT is safe and feasible (I). Both bio-active and endothelial progenitor cell capturing stents showed near-complete endothelialisation after one-month follow-up, which is desirable when prolonged dual anti-platelet therapy needs to be avoided after stenting (II and III). Endothelialisation of bio-active stents showed a predictable pattern at mid-term and long-term follow up (IV and V). Endothelialisation of everolimus-eluting stents was not complete at 9 months follow-up, which may suggest that interruption of dual antiplatelet therapy at this time point may not be safe (IV). Finally, delayed vascular healing may be present in patients treated with paclitaxel-eluting stents as long as 4 years from implantation, which reinforces the previously raised concerns on the long-term safety of this device (V).