The Regulation of Skeletal and Cardiac Muscle Blood Flow in Humans. Studies by positron emission tomography with special reference to exercise, adenosine and nitric oxide

Virtually every cell and organ in the human body is dependent on a proper oxygen supply. This is taken care of by the cardiovascular system that supplies tissues with oxygen precisely according to their metabolic needs. Physical exercise is one of the most demanding challenges the human circulatory system can face. During exercise skeletal muscle blood flow can easily increase some 20-fold and its proper distribution to and within muscles is of importance for optimal oxygen delivery. The local regulation of skeletal muscle blood flow during exercise remains little understood, but adenosine and nitric oxide may take part in this process. In addition to acute exercise, long-term vigorous physical conditioning also induces changes in the cardiovasculature, which leads to improved maximal physical performance. The changes are largely central, such as structural and functional changes in the heart. The function and reserve of the heart’s own vasculature can be studied by adenosine infusion, which according to animal studies evokes vasodilation via it’s a_2A receptors. This has, however, never been addressed in humans in vivo and also studies in endurance athletes have shown inconsistent results regarding the effects of sport training on myocardial blood flow. This study was performed on healthy young adults and endurance athletes and local skeletal and cardiac muscle blod flow was measured by positron emission tomography. In the heart, myocardial blood flow reserve and adenosine A_2A receptor density, and in skeletal muscle, oxygen extraction and consumption was also measured. The role of adenosine in the control of skeletal muscle blood flow during exercise, and its vasodilator effects, were addressed by infusing competitive inhibitors and adenosine into the femoral artery. The formation of skeletal muscle nitric oxide was also inhibited by a drug, with and without prostanoid blockade. As a result and conclusion, it can be said that skeletal muscle blood flow heterogeneity decreases with increasing exercise intensity most likely due to increased vascular unit recruitment, but exercise hyperemia is a very complex phenomenon that cannot be mimicked by pharmacological infusions, and no single regulator factor (e.g. adenosine or nitric oxide) accounts for a significant part of exercise-induced muscle hyperemia. However, in the present study it was observed for the first time in humans that nitric oxide is not only important regulator of the basal level of muscle blood flow, but also oxygen consumption, and together with prostanoids affects muscle blood flow and oxygen consumption during exercise. Finally, even vigorous endurance training does not seem to lead to supranormal myocardial blood flow reserve, and also other receptors than A_2A mediate the vasodilator effects of adenosine. In respect to cardiac work, atheletes heart seems to be luxuriously perfused at rest, which may result from reduced oxygen extraction or impaired efficiency due to pronouncedly enhanced myocardial mass developed to excel in strenuous exercise.

Early Detection of Alzheimer's Disease Beta-amyloid Pathology -Applicability of Positron Emission Tomography with the Amyloid Radioligand 11C-PIB

Early Detection of Alzheimer's Disease Beta-amyloid Pathology -Applicability of Positron Emission Tomography with the Amyloid Radioligand ¹¹C-PIB Accumulation of beta amyloid (Abeta) in the brain is characteristic for Alzheimer’s disease (AD). Carbon-11 labeled 2-(4’-methylaminophenyl)-6-hydroxybenzothiazole (¹¹C-PIB) is a novel positron emission tomography (PET) amyloid imaging agent that appears to be applicable for in vivo Abeta plaque detection and quantitation. The biodistribution and radiation dosimetry of ¹¹C-PIB were investigated in 16 healthy subjects. The reproducibility of a simplified ¹¹C-PIB quantitation method was evaluated with a test-retest study on 6 AD patients and 4 healthy control subjects. Brain ¹¹C-PIB uptake and its possible association with brain atrophy rates were studied over a two-year follow-up in 14 AD patients and 13 healthy controls. Nine monozygotic and 8 dizygotic twin pairs discordant for cognitive impairment and 9 unrelated controls were examined to determine whether brain Abeta accumulation could be detected with ¹¹C-PIB PET in cognitively intact persons who are at increased genetic risk for AD. The highest absorbed radiation dose was received by the gallbladder wall (41.5 mjuGy/MBq). About 20 % of the injected radioactivity was excreted into urine, and the effective whole-body radiation dose was 4.7 mjuSv/MBq. Such a dose allows repeated scans of individual subjects. The reproducibility of the simplified ¹¹C-PIB quantitation was good or excellent both at the regional level (VAR 0.9-5.5 %) and at the voxel level (VAR 4.2-6.4 %). ¹¹C-PIB uptake did not increase during 24 months’ follow-up of subjects with mild or moderate AD, even though brain atrophy and cognitive decline progressed. Baseline neocortical ¹¹C-PIB uptake predicted subsequent volumetric brain changes in healthy control subjects (r = 0.725, p = 0.005). Cognitively intact monozygotic co-twins – but not dizygotic co-twins – of memory-impaired subjects exhibited increased ¹¹C-PIB uptake (117-121 % of control mean) in their temporal and parietal cortices and the posterior cingulate (p<0.05), when compared with unrelated controls. This increased uptake may be representative of an early AD process, and genetic factors seem to play an important role in the development of AD-like Abeta plaque pathology. ¹¹C-PIB PET may be a useful method for patient selection and follow-up for early-phase intervention trials of novel therapeutic agents. AD might be detectable in high-risk individuals in its presymptomatic stage with ¹¹C-PIB PET, which would have important consequences both for future diagnostics and for research on disease-modifying treatments.

Akustisen emission anturin signaalin esikäsittelypiirin selvittäminen ja prototyypin toteuttaminen

Tämän työn tavoitteena oli selvittää ja toteuttaa esikäsittelypiirin prototyyppi akustisen emission anturin signaalille. Toteutettu esikäsittelypiiri toimii yksipuoleisella käyttöjännitteellä. Työssä käydään läpi esikäsittelypiirin suunnitteluun liittyvät vaiheet laskelmien ja simulaatioiden muodossa. Lisäksi työssä esitetään mittaustulokset esikäsittelypiirin toiminnasta.

Imaging of Dopamine and Serotonin Transporters. Pre-clinical Studies with Radiotracers for Positron Emission Tomography

The action of the neurotransmitters dopamine (DA) and serotonin (5-HT) at synapses is terminated by their rapid reuptake into presynaptic nerve endings via plasma membrane dopamine (DAT) and serotonin (SERT) transporters. Alterations in the function of these transporters have been suggested as a feature of several neurological and neuropsychiatric diseases, such as Parkinson’s disease (PD), depression, and anxiety. A suitable clinical method for studying these transporters non-invasively in vivo is positron emission tomography (PET) utilizing radiopharmaceuticals (tracers) labelled with short-lived positron-emitting radionuclides. The aim of this study was to evaluate in rats two novel radiotracers, [¹⁸F]beta -CFT-FP and ¹⁸FFMe-McN, for imaging DAT and SERT, respectively, using in vitro, ex vivo and in vivo methods. Substituting an N-methyl in [¹⁸F]beta-CFT, a well known DAT tracer, with a ¹⁸Ffluoropropyl group significantly changed the properties of the tracer. [¹⁸F]beta- CFT showed slow kinetics and metabolism, and a high specific uptake in the striatum, whereas [¹⁸F]beta-CFT-FP showed fast kinetics and metabolism, and a moderate specific uptake in the striatum. [¹⁸F]betaCFT-FP was selective for DAT; but [¹⁸F]beta-CFT also bound to the noradrenaline transporter. [¹⁸F]beta-CFT-FP may be a suitable PET tracer for imaging the striatal DAT sites, but a tracer with a higher affinity is needed for imaging extrastriatal DAT sites. In rats, ¹⁸FFMe-McN showed high target-to-non-target ratios, specificity and selectivity for SERT, but slow kinetics. However, ¹⁸FFMe-McN reveals potential for imaging SERT, at least in pre-clinical studies. In addition, the sensitivities of [¹⁸F]beta CFT and [¹⁸ F]FDOPA (a precursor of DA) for detecting mild nigrostriatal hypofunction were compared in an animal model of PD. The uptake of [¹⁸F]FDOPA was significantly affected by compensatory effects in dopaminergic cells, whereas [¹⁸F]beta-CFT was more sensitive and therefore more suitable for PET studies of mild dopaminergic symptoms. In conclusion, both novel tracers, [¹⁸F]-CFT-FP and ¹⁸FFMe-McN, have potential, but are not optimal PET tracers for DAT and SERT imaging in rats, respectively. [¹⁸F]beta-CFT is superior to [18F]FDOPA for imaging mild nigral lesions in rat brains.

Mild Cognitive Impairment and Early Detection of Alzheimer`s Disease. A Positron Emission Tomography Study

Alzheimer`s disease (AD) is characterised neuropathologically by the presence of extracellular amyloid plaques, intraneuronal neurofibrillary tangles, and cerebral neuronal loss. The pathological changes in AD are believed to start even decades before clinical symptoms are detectable. AD gradually affects episodic memory, cognition, behaviour and the ability to perform everyday activities. Mild cognitive impairment (MCI) represents a transitional state between normal aging and dementia disorders, especially AD. The predictive accuracy of the current and commonly used MCI criteria devide this disorder into amnestic (aMCI) and non-amnestic (naMCI) MCI. It seems that many individuals with aMCI tend to convert to AD. However many MCI individuals will remain stable and some may even recover. At present, the principal drugs for the treatment of AD provide only symptomatic and palliative benefits. Safe and effective mechanism-based therapies are needed for this devastating neurodegenerative disease of later life. In conjunction with the development of new therapeutic drugs, tools for early detection of AD would be important. In future one of the challenges will be to detect at an early stage these MCI individuals who will convert to AD. Methods which can predict which MCI subjects will convert to AD will be much more important if the new drug candidates prove to have disease-arresting or even disease–slowing effects. These types of drugs are likely to have the best efficacy if administered in the early or even in the presymptomatic phase of the disease when the synaptic and neuronal loss has not become too widespread. There is no clinical method to determine with certainly which MCI individuals will progress to AD. However there are several methods which have been suggested as predictors of conversion to AD, e.g. increased [11C] PIB uptake, hippocampal atrophy in MRI, low CSF A beta 42 level, high CSF tau-protein level, apolipoprotein E (APOE) ε4 allele and impairment in episodic memory and executive functions. In the present study subjects with MCI appear to have significantly higher [¹¹C] PIB uptake vs healthy elderly in several brain areas including frontal cortex, the posterior cingulate, the parietal and lateral temporal cortices, putamen and caudate. Also results from this PET study indicate that over time, MCI subjects who display increased [¹¹C] PIB uptake appear to be significantly more likely to convert to AD than MCI subjects with negative [¹¹C] PIB retention. Also hippocampal atrophy seems to increase in MCI individuals clearly during the conversion to AD. In this study [¹¹C] PIB uptake increases early and changes relatively little during the AD process whereas there is progressive hippocampal atrophy during the disease. In addition to increased [¹¹C] PIB retention and hippocampal atrophy, the status of APOE ε4 allele might contribute to the conversion from MCI to AD.

Pintataistelualusten kehittämisen haasteet 2000-luvun alussa : Yhdysvaltojen laivaston Littoral Combat Ship- ja hävittäjähankkeiden laivatekniikka

Tässä diplomityössä tutkittiin Yhdysvaltojen laivaston DDG-1000-hävittäjä- ja Littoral Combat Ship (LCS) -hankkeissa kehitettävien pintataistelualusten laivateknisten ratkaisujen vaikutusta alusten ominaisuuksiin. Tutkimuksen painopiste oli laivatekniikassa, mutta tarkastelu kiinnitettiin käynnissä oleviin hankkeisiin. Aineiston keräämisen menetelmänä käytettiin kirjallisuustutkimusta. Aineisto analysoitiin aineistolähtöisesti, ja laivatekniikan analysoinnin mallina käytettiin laivan konseptisuunnittelun keskeisiä osa-alueita. Laivatekniikkaa analysoitiin vertailemalla aiempien ja uusien alusten teknisiä ratkaisuja. Tutkimusraportti laadittiin soveltamalla prosessikirjoittamista. DDG-1000- ja LCS-hankkeiden vaatimukset perustuivat varsin tarkasti määriteltyihin tehtäviin osana rannikkomerioperointia. Uusilla hankintatavoilla ei kyetty hallitsemaan hankkeiden kustannuksia. DDG-1000-hankkeen kustannusten kasvu vaikutti johtuvan toimittajien välisen kilpailun puuttumisen lisäksi lukuisista uusista teknisistä järjestelmistä ja LCS-hankkeessa nopean hankintatavan aiheuttamista tekijöistä. DDG-1000-hankkeessa päädyttiin vain kolmen aluksen hankintaan ja vanhemman DDG-51-hävittäjän tuotannon uudelleen aloittamiseen. Toistaiseksi LCS-hankkeen 55 aluksen tavoitteessa ei ole tapahtunut muutoksia. LCS-1:n runkoratkaisu on puoliliukuva teräsrunko ja LCS-2:n alumiininen trimaraanirunko. Suuresta nopeudesta johtuen LCS:ien koneistotehot ovat samaa suuruusluokkaan kuin hävittäjillä, tosin LCS-2:n kulkuvastus on pienempi kuin LCS-1:n suurella nopeudella. Hitaammilla nopeuksilla LCS:ien runkojen ja vesisuihkupropulsion hyötysuhteet arvioitiin heikommiksi kuin uppoumarunkoisella fregatilla. LCS:issä on suuret modulaarisesta taistelujärjestelmästä ja alusten ulkopuolella operoitavista järjestelmistä johtuvat lasti- ja kansitilat. LCS-2:n runkoratkaisu on erittäin vakaa. Nopeat alukset ovat herkkiä painon muutoksille. Painavamman LCS-1:n kantavuus arvioitiin alhaiseksi. LCS-2:n painoa on hallittu kevyellä rakenteella. Sen osalta epävarmuutta on aiheuttanut poikittaisten aaltokuormien kantokyky. LCS:ien taistelunkestävyys on kyseenalaistettu. DDG-1000:n sisäänpäin kallistetuilla kyljillä varustettu runkoratkaisu perustui häivevaatimuksiin. Aluksen suureen kokoon on vaikuttanut keinunnanvaimennustankkien ja kokonaan sähköisen koneiston soveltaminen. Poikkeava runkomuoto ja suuri koko ovat mahdollistaneet uudenlaisen yleisjärjestelyn suunnittelun. Sähköisellä koneistolla on päästy pienempään kaasuturbiinien lukumäärään sekä joustavaan koneistojen käyttöprofiiliin. Runkomuodon vauriovakavuus, riski alavirtausperän paineiskuihin ja epävarmuus dynaamisesta vakavuudesta suuressa aallokossa ovat aiheuttaneet epäilyksiä aluksen merikelpoisuudesta. Suhteellisen alhaisen tehon perusteella aluksen kulkuvastusominaisuudet vaikuttivat hyviltä. Sekä LCS että DDG-1000 ovat tehtäviin optimoinnista johtuen eräänlaisia erikoisaluksia, jotka eivät sellaisenaan sovi yleiskäyttöisten pintataistelualusten esikuviksi. Yleisesti ottaen tutkimuksen aikana syntyi näkemys, jonka mukaan taistelualuksen tehtävät tulisi määritellä riittävän väljästi, ja siten varmistaa, että alus on hyvä, mutta ei välttämättä paras, koko elinjaksonsa ajan.

In vivo imaging of vascular adhesion protein 1 - preclinical studies with positron emission tomography

The golden standard in nuclear medicine imaging of inflammation is the use of radiolabeled leukocytes. Although their diagnostic accuracy is good, the preparation of the leukocytes is both laborious and potentially hazardous for laboratory personnel. Molecules involved in leukocyte migration could serve as targets for the development of inflammation imaging agents. An excellent target would be a molecule that is absent or expressed at low level in normal tissues, but is induced or up-regulated at the site of inflammation. Vascular adhesion protein-1 (VAP-1) is a very promising target for in vivo imaging, since it is translocated to the endothelial cell surface when inflammation occurs. VAP-1 functions as an endothelial adhesion molecule that participates in leukocyte recruitment to inflamed tissues. Besides being an adhesion molecule, VAP-1 also has enzymatic activity. In this thesis, the targeting of VAP-1 was studied by using Gallium-68 (68Ga) labeled peptides and an Iodine-124 (124I) labeled antibody. The peptides were designed based on molecular modelling and phage display library searches. The new imaging agents were preclinically tested in vitro, as well as in vivo in animal models. The most promising imaging agent appeared to be a peptide belonging to the VAP-1 leukocyte ligand, Siglec-9 peptide. The 68Ga-labeled Siglec-9 peptide was able to detect VAP-1 positive vasculature in rodent models of sterile skin inflammation and melanoma by positron emission tomography. In addition to peptides, the 124I-labeled antibody showed VAP-1 specific binding both in vitro and in vivo. However, the estimated human radiation dose was rather high, and thus further preclinical studies in disease models are needed to clarify the value of this imaging agent. Detection of VAP-1 on endothelium was demonstrated in these studies and this imaging approach could be used in the diagnosis of inflammatory conditions as well as melanoma. These studies provide a proof-of-concept for PET imaging of VAP-1 and further studies are warranted.

Operointialueen huomioiminen risteilylaivan sähkötaseessa

Kiristyvät päästörajoitukset ja muuttuvat säädökset ovat muokanneet laivanrakennusalaa energiatehokkaampaan ja ympäristöystävällisempään suuntaan. Energiatehokkuutta tutkitaan yksittäisistä laiteratkaisuista laivan operointitasolle asti. Tämä työ on tehty osana STX Finland Oy:n laivojen energiatehokkuuden tutkimusta. Työn tarkoituksena oli uudistaa laivojen sähkötaseen laskennassa käytettyjä kuormitustaulukoita ja kehittää operointialueen vaikutuksia huomioiva laskentamenetelmä. Uudistuksen taustalla oli tieto operointialueiden ympäristöolosuhteiden vaikutuksista sähkönkulutukseen ja työn tarkoituksena oli mahdollistaa suunnittelun myöhäisemmässä vaiheessa tehtävä operointialuekohtainen sähkönkulutustarkastelu. Sähkötaseen laskenta haluttiin vastaamaan enemmän todellista sähkönkulutusta. Aikaisemmin käytetystä mitoitusperusteisesta laskennasta haluttiin siirtyä todellisempien kuormien arviointiin laitteiden ja muuntajien turhan ylimitoituksen poistamiseksi. Kuormitustaulukoiden toimintaa yksinkertaistettiin ja taulukoista tehtiin helpommin mukautuvia, jotta erilaisten operointitilanteiden vertailu olisi mahdollista. Perinteisen taselaskennan rinnalle kehitettiin operointialueiden vaikutuksia huomioivat laskentataulukot. Uudet taulukot huomioivat komponenttien sähkönkulutuksen prosentuaalisen muutoksen operointialueittain sekä yksilöllisesti että kulutusryhmittäin. Laskentataulukoiden yhteyteen tehtiin kuvaajat havainnollistamaan alueittaisia kulutuseroja.

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.

Model-Based Tracking Initialization in Ship Building Environment

An augmented reality (AR) device must know observer’s location and orientation, i.e. observer’s pose, to be able to correctly register the virtual content to observer’s view. One possible way to determine and continuously follow-up the pose is model-based visual tracking. It supposes that a 3D model of the surroundings is known and that there is a video camera that is fixed to the device. The pose is tracked by comparing the video camera image to the model. Each new pose estimate is usually based on the previous estimate. However, the first estimate must be found out without a prior estimate, i.e. the tracking must be initialized, which in practice means that some model features must be identified from the image and matched to model features. This is known in literature as model-to-image registration problem or simultaneous pose and correspondence problem. This report reviews visual tracking initialization methods that are suitable for visual tracking in ship building environment when the ship CAD model is available. The environment is complex, which makes the initialization non-trivial. The report has been done as part of MARIN project.

The effect of environmentally differentiated port fees to shipping companies’ environmental investments

The pressure has grown to develop cost-effective emission reduction strategies in the Baltic Sea. The forthcoming stringent regulations of the International Maritime Organization for reducing harmful emissions of shipping in the Baltic Sea are causing increasing expenses for the operators. A market-based attitude towards pricing of economic incentives could be seen as a new approach for a successful application for the additional emission reduction of nitrogen oxides (NOx). In this study the aim is to understand the phenomenon of environmentally differentiated port fees and its effects on shipping companies’ emission reduction investments. The goal is to examine empirically the real-life effects of the possible environmental differentiated port fee system and the effect of environmentally differentiated port fees on NOx reduction investments in the Baltic Sea. The research approach of this study is nomothetical. In this study research questions are answered by analyzing the broad database of the Baltic Sea fleet. Also the framework of theory is confirmed and plays an important role in analyzing the research problem. Existing investment costs of NOx emission reduction technology to ship owners are estimated and compared to investment costs with granted discounts added to the cash flows. The statistical analysis in this study is descriptive. The major statistic examination of this study is the calculation of the net present values of investments with different port fee scenarios. This is done to investigate if the NOx technology investments could be economically reasonable. Based on calculations it is clear that the effect of environmentally differentiated port fees is not adequate to compensate the total investment costs for NOx reduction. If the investment decision is made only with profitability considerations, sources will prefer to emission abatement as long as incomes from the given subsidy exceeds their abatement costs. Despite of the results, evidence was found that shipping companies are nevertheless willing to invest on voluntary emission abatement technology. In that case, investment decision could be made with criteria of, for example, sustainable strategy or brand image. Combined fairway and port fee system or governmental regulations and recommendation could also function as additional incentives to compensate the investment costs. Also, the results imply that the use of NPV is not necessarily the best method to evaluate environmental investments. If the calculations would be done with more environmental methods the results would probably be different.

The Straits of Seniavine : Behring Straits by the U.S. Ship Vincennes

Kartta kuuluu A. E. Nordenskiöldin kokoelmaan

Potential for Greenhouse Gas Emission Reductions by Using Biomethane as a Road Transportation Fuel

The aim of this thesis is to study whether the use of biomethane as a transportation fuel is reasonable from climate change perspective. In order to identify potentials and challenges for the reduction of greenhouse gas (GHG) emissions, this dissertation focuses on GHG emission comparisons, on feasibility studies and on the effects of various calculation methodologies. The GHG emissions calculations are carried out by using life cycle assessment (LCA) methodologies. The aim of these LCA studies is to figure out the key parameters affecting the GHG emission saving potential of biomethane production and use and to give recommendations related to methodological choices. The feasibility studies are also carried out from the life cycle perspective by dividing the biomethane production chain for various operators along the life cycle of biomethane in order to recognize economic bottlenecks. Biomethane use in the transportation sector leads to GHG emission reductions compared to fossil transportation fuels in most cases. In addition, electricity and heat production from landfill gas, biogas or biomethane leads to GHG reductions as well. Electricity production for electric vehicles is also a potential route to direct biogas or biomethane energy to transportation sector. However, various factors along the life cycle of biomethane affect the GHG reduction potentials. Furthermore, the methodological selections have significant effects on the results. From economic perspective, there are factors related to different operators along the life cycle of biomethane, which are not encouraging biomethane use in the transportation sector. To minimize the greenhouse gas emissions from the life cycle of biomethane, waste feedstock should be preferred. In addition, energy consumption, methane leakages, digestate utilization and the current use of feedstock or biogas are also key factors. To increase the use of biomethane in the transportation sector, political steering is needed to improve the feasibility for the operators. From methodological perspective, it is important to recognize the aim of the life cycle assessment study. The life cycle assessment studies can be divided into two categories: 1.) To produce average GHG information of biomethane to evaluate the acceptability of biomethane use compared to fossil transportation fuels. 2.) To produce GHG information of biomethane related to actual decision-making situations. This helps to figure out the actual GHG emission changes in cases when feedstock, biogas or biomethane are already in other use. For example directing biogas from electricity production to transportation use does not necessarily lead to additional GHG emission reductions. The use of biomethane seems to have a lot of potential for the reduction of greenhouse gas emissions as a transportation fuel. However, there are various aspects related to production processes, to the current use of feedstock or biogas and to the feasibility that have to be taken into account.