Imaging of the Vulnerable Atherosclerotic Plaque. Pre-Clinical Evaluation of PET Tracers for Vascular Inflammation

Atherosclerosis is a vascular inflammatory disease causing coronary artery disease, myocardial infarct and stroke, the leading causes of death in Finland and in many other countries. The development of atherosclerotic plaques starts already in childhood and is an ongoing process throughout life. Rupture of a plaque and the following occlusion of the vessel is the main reason for myocardial infarct and stroke, but despite extensive research, the prediction of rupture remains a major clinical problem. Inflammation is considered a key factor in the vulnerability of plaques to rupture. Measuring the inflammation in plaques non-invasively is one potential approach for identification of vulnerable plaques. The aim of this study was to evaluate tracers for positron emission tomography (PET) imaging of vascular inflammation. The studies were performed with a mouse model of atherosclerosis by using ex vivo biodistribution, autoradiography and in vivo PET and computed tomography (CT). Several tracers for inflammation activity were tested and compared with the morphology of the plaques. Inflammation in the atherosclerotic plaques was evaluated as expression of active macrophages. Systematic analysis revealed that the uptake of 18F-FDG and 11C-choline, tracers for metabolic activity in inflammatory cells, was more prominent in the atherosclerotic plaques than in the surrounding healthy vessel wall. The tracer for αvβ3 integrin, 18Fgalacto- RGD, was also found to have high potential for imaging inflammation in the plaques. While 11C-PK11195, a tracer targeted to receptors in active macrophages, was shown to accumulate in active plaques, the target-to-background ratio was not found to be ideal for in vivo imaging purposes. In conclusion, tracers for the imaging of inflammation in atherosclerotic plaques can be tested in experimental pre-clinical settings to select potential imaging agents for further clinical testing. 18F-FDG, 18F-galacto-RGD and 11C-choline choline have good properties, and further studies to clarify their applicability for atherosclerosis imaging in humans are warranted.

Inversion and assimilation methods with applications in geophysical remote sensing

Stratospheric ozone can be measured accurately using a limb scatter remote sensing technique at the UV-visible spectral region of solar light. The advantages of this technique includes a good vertical resolution and a good daytime coverage of the measurements. In addition to ozone, UV-visible limb scatter measurements contain information about NO2, NO3, OClO, BrO and aerosols. There are currently several satellite instruments continuously scanning the atmosphere and measuring the UVvisible region of the spectrum, e.g., the Optical Spectrograph and Infrared Imager System (OSIRIS) launched on the Odin satellite in February 2001, and the Scanning Imaging Absorption SpectroMeter for Atmospheric CartograpHY (SCIAMACHY) launched on Envisat in March 2002. Envisat also carries the Global Ozone Monitoring by Occultation of Stars (GOMOS) instrument, which also measures limb-scattered sunlight under bright limb occultation conditions. These conditions occur during daytime occultation measurements. The global coverage of the satellite measurements is far better than any other ozone measurement technique, but still the measurements are sparse in the spatial domain. Measurements are also repeated relatively rarely over a certain area, and the composition of the Earth’s atmosphere changes dynamically. Assimilation methods are therefore needed in order to combine the information of the measurements with the atmospheric model. In recent years, the focus of assimilation algorithm research has turned towards filtering methods. The traditional Extended Kalman filter (EKF) method takes into account not only the uncertainty of the measurements, but also the uncertainty of the evolution model of the system. However, the computational cost of full blown EKF increases rapidly as the number of the model parameters increases. Therefore the EKF method cannot be applied directly to the stratospheric ozone assimilation problem. The work in this thesis is devoted to the development of inversion methods for satellite instruments and the development of assimilation methods used with atmospheric models.

De sangvisuga

Invocatio: KREIKKAA Alpha & omega.

Laulu valon sodassa

Soitinnus: lauluääni, piano.

Salon keskusta-alueen tulvasuojelu : Tulvasuojelutoimenpiteiden mitoitus ja arviointi

Uskelanjoki virtaa Salon kaupungin läpi ja varsinkin jääpato tulvatilanteissa tulvavedenkorkeudet uhkaavat nousta maa-alueille. Tässä työssä tutkittiin valittujen tulvasuojelutoimenpiteiden vaikutuksia tulvavedenkorkeuksiin Uskelanjoessa sekä Salon kaupungin keskusta-alueella. Tavoitteena oli löytää Uskelanjoen tulvimisen ehkäisyyn kustannustehokas ratkaisu. Työssä mallinnettiin Uskelanjoen vedenkorkeuksia yksidimensionaalisesti käyttäen HEC-RAS -mallia. Mallinnus suoritettiin mitoitustulvalla tulvasuojelutoimenpiteille, jotka olivat jäidenpidätysrakennelmien rakentaminen, ruoppaus, pengerrys sekä näiden vaihtoehtojen yhdistelmät. Mallinnuksesta saatujen tulvavedenkorkeuksien avulla laadittiin tarkastellulta uomaosuudelta tulvavaarakartat sekä tulvavahinkoarviot. Näiden tietojen pohjalta voitiin vaihtoehtojen hyötyjä vertailla käyttämällä kustannus-hyötyanalyysia. Kustannus-hyötyanalyysin tuloksista havaittiin, että jäidenpidätysrakennelmat osoittautuivat parhaaksi tulvasuojeluvaihtoehdoksi Uskelanjoessa. Muutkin työssä tutkitut vaihtoehdot osoittautuivat kannattaviksi. Epävarmuuden kumuloituminen vedenkorkeuksien mallinnuksesta hyötyjen ja haittojen arviointiin luo oman epävarmuutensa tässä työssä laskettuihin arvoihin. Tätä epävarmuutta on tutkittu työssä käyttämällä herkkyysanalyysia. Herkkyysanalyysin tuloksia tarkastelemalla jäidenpidätysrakennelmien rakentaminen osoittautui kaikkein riskivapaimmaksi vaihtoehdoksi Uskelanjoen tulvasuojelussa.

Modelling of changes in electricity end-use and their impacts on electricity distribution

The electricity distribution sector will face significant changes in the future. Increasing reliability demands will call for major network investments. At the same time, electricity end-use is undergoing profound changes. The changes include future energy technologies and other advances in the field. New technologies such as microgeneration and electric vehicles will have different kinds of impacts on electricity distribution network loads. In addition, smart metering provides more accurate electricity consumption data and opportunities to develop sophisticated load modelling and forecasting approaches. Thus, there are both demands and opportunities to develop a new type of long-term forecasting methodology for electricity distribution. The work concentrates on the technical and economic perspectives of electricity distribution. The doctoral dissertation proposes a methodology to forecast electricity consumption in the distribution networks. The forecasting process consists of a spatial analysis, clustering, end-use modelling, scenarios and simulation methods, and the load forecasts are based on the application of automatic meter reading (AMR) data. The developed long-term forecasting process produces power-based load forecasts. By applying these results, it is possible to forecast the impacts of changes on electrical energy in the network, and further, on the distribution system operator’s revenue. These results are applicable to distribution network and business planning. This doctoral dissertation includes a case study, which tests the forecasting process in practice. For the case study, the most prominent future energy technologies are chosen, and their impacts on the electrical energy and power on the network are analysed. The most relevant topics related to changes in the operating environment, namely energy efficiency, microgeneration, electric vehicles, energy storages and demand response, are discussed in more detail. The study shows that changes in electricity end-use may have radical impacts both on electrical energy and power in the distribution networks and on the distribution revenue. These changes will probably pose challenges for distribution system operators. The study suggests solutions for the distribution system operators on how they can prepare for the changing conditions. It is concluded that a new type of load forecasting methodology is needed, because the previous methods are no longer able to produce adequate forecasts.