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Uvod: Nevrodegenerativne bolezni možganov so kronična, napredujoča in neozdravljiva obolenja, ki se klinično izrazijo s kognitivnim upadom in/ali motnjami gibanja. Zgodnja klinična diagnostična natančnost je relativno nizka. V pomoč pri natančnejši zgodnejši diagnozi in razlikovanju med njimi se vse bolj uveljavljajo različni biološki označevalci, biokemični in slikovni. Med slednje sodi tudi funkcijsko slikanje možganov s 18F-FDG PET, s katerim lahko merimo presnovo glukoze, ki odraža sinaptično aktivnost nevronov. Presnova glukoze v možganih se spremeni že v zelo zgodnjih fazah nevrodegenerativnih bolezni. Analiza 18F-FDG PET slik možganov nam lahko pomaga pri razlikovanju med različnimi nevrodegenerativnimi sindromi, ki so lahko klinično zelo podobni, in pri spoznavanju patofizioloških procesov v možganih. Z multivariatno statistično obdelavo 18F-FDG PET slik lahko identificiramo za nevrodegenerativni sindrom specifične presnovne vzorce funkcijsko povezanih možganskih področij, ki predstavljajo presnovni biološki označevalec določenega nevrodegenerativnega sindroma. Cilji doktorske disertacije so: (1) identifikacija in validacija presnovnega vzorca, specifičnega za sporadično Creutzfeldt-Jakobovo bolezen, ter preučitev njegovih lastnosti (2) analiza diagnostične natančnosti klinične diagnoze nevrodegenerativnih parkinsonizmov v primerjavi z avtomatsko diagnozo na podlagi analize 18F-FDG PET slik (3) analiza izraženosti in specifičnosti motoričnega in kognitivnega presnovnega vzorca, značilnega za Parkinsonovo bolezen (PB), v različnih fazah bolezni in pri drugih parkinsonizmih. Metode: V retrospektivni raziskavi smo za dosego vseh treh ciljev analizirali klinične podatke in 18F-FDG PET slike možganov 784 preiskovancev: 29 bolnikov s Creutzfeldt-Jakobovo boleznijo (CJB), 26 bolnikov z Alzheimerjevo demenco (AD), 20 bolnikov z vedenjsko različico frontotemporalne demence bvFTD), 356 bolnikov s PB, 125 bolnikov z multisistemsko atrofijo, 113 bolnikov s progresivno supranuklearno parezo in 115 zdravih preiskovancev (ZP) iz petih centrov. Vsi preiskovanci so opravili 18F-FDG PET slikanje možganov. Po predpripravi slik smo za dosego cilja (1) z metodo skalirani subprofilni model, zasnovan na analizi glavnih komponent (SSM-PCA), analizirali 18F-FDG PET slike možganov bolnikov s CJB in ZP in identificirali ter validirali vzorec, specifičen za sporadično CJB (CJDRP) za dosego cilja (2) smo določili natančnost klinične diagnoze parkinsonizmov 12 mesecev po slikanju in jo primerjali z diagnozo, ki jo izračuna avtomatski logistični diferencialno diagnostični algoritem na podlagi analize 18F-FDG PET slik, kar je bil diagnostični zlati standard in za dosego cilja (3) smo analizirali razliko v izraženosti motoričnega in kognitivnega presnovnega možganskega vzorca, specifičnega za PB v različnih fazah PB, jo primerjali z drugimi parkinsonskimi sindromi in ovrednotili njen pomen v diferencialni diagnozi parkinsonizmov. Rezultati: (1) Identificirali in validirali smo CJDRP in ugotovili signifikantno korelacijo med njegovo izraženostjo in kliničnimi lastnostmi bolnikov. Dokazali smo, da je vzorec specifičen za CJB. (2) Primerjava klinično postavljene diagnoze z avtomatsko je razkrila njeno 94,7-% občutljivost, 83,3-% specifičnost, 81,8-% pozitivno napovedno vrednost (PNV) in 95,2-% negativno napovedno vrednost (NNV) za diagnozo PB ter 88,2-% občutljivost, 76,9-% specifičnost, 71,4-% PNV in 90,9-% NNV za diagnozo atipičnih parkinsonizmov. (3) Razmerje med motoričnim in kognitivnim presnovnim vzorcem pri bolnikih s PB je bilo konstantno. Razlika med obema vzorcema je z napredovanjem bolezni vztrajno naraščala v več presečnih in longitudinalnih kohortah. Poleg tega je kombinacija motoričnega vzorca in razlike med obema vzorcema ustrezno razlikovala bolnike s PB od atipičnih parkinsonizmov. Zaključek: V tej disertaciji smo identificirali nov multivariatni presnovni vzorec možganov, specifičen za CJB, ki ima pomemben potencial v nadaljnjih raziskavah nevrodegenerativnih bolezni. Dokazali smo superiornost avtomatske diagnoze, temelječe na 18F-FDG PET, v primerjavi s klinično. Na podlagi razmerij med motoričnim in kognitivnim presnovnim vzorcem pri PB pa lahko sklepamo o napredovanju okvare možganskih omrežij, ki je skladna z Braakovo hipotezo. S to raziskavo smo omogočili nov vpogled v patofiziologijo nevrodegeneracije pri CJB, PB in atipičnih parkinsonizmih ter postavili podlago za uvedbo natančne diagnostične metode, ki temelji na avtomatizirani oceni multivariatnih možganskih presnovnih vzorcev, v klinično prakso. Oboje je predpogoj za raziskovanje potencialnih novih zdravljenj nevrodegenerativnih bolezni. Omenjene omrežne analitične metode se vse bolj uveljavljajo pri raziskovanju možganskih omrežij in klinični diagnostiki nevrodegenerativnih bolezni. Raziskave, ki so del te doktorske disertacije, so prispevale v zakladnico skupnega znanja o funkcijskih možganskih omrežjih, ki ga natančneje povzemamo v zadnjem poglavju. Background: Neurodegenerative brain disorders are chronic, progressive, and incurable diseases that clinically manifest with cognitive decline and/or movement disorders. Early clinical diagnostic accuracy is relatively low. In recent years, various imaging biomarkers were studied to gain better diagnostic accuracy in early disease stages and to distinguish among similar syndromes. Functional brain imaging with 18F-FDG PET measures regional glucose metabolism, which reflects the synaptic activity of neurons. Brain glucose metabolism is altered already at early stages of neurodegenerative diseases. 18F-FDG PET brain analysis can help us to differentiate between different neurodegenerative syndromes and to learn about pathophysiological processes in the brain. Furthermore, multivariate statistical analysis of 18F-FDG PET images enable us to identify syndrome-specific metabolic patterns of functionally interconnected brain areas that serve as a metabolic biomarker of a particular neurodegenerative syndrome. Aims of this dissertation were (1) to identify and validate a metabolic pattern specific for sporadic Creutzfeldt-Jakob disease (CJD) and to study its properties (2) analysis of the diagnostic accuracy of the clinical diagnosis of neurodegenerative parkinsonisms in comparison to automated 18F-FDG PET based diagnosis and (3) analysis of motor and cognitive metabolic patterns characteristic for Parkinson's disease (PD) and relationship between them at different stages of the disease and in comparison to other parkinsonian syndromes. Methods: In a retrospective study, we analyzed clinical data and 18F-FDG PET brain images of 784 subjects: 29 patients with CJD, 26 patients with Alzheimer’s dementia (AD), 20 patients with behavioral variant of frontotemporal dementia (bvFTD), 356 patients with PD, 125 patients with multisystem atrophy, 113 patients with progressive supranuclear paresis (the latter two entities combined into an atypical parkinsonian syndrome (APS) group) and 115 healthy subjects (HS). All subjects underwent 18F-FDG PET brain imaging. After image preprocessing, we (1) analyzed the 18F-FDG PET brain images of patients with CJD and HS using a scaled subprofile modelling – principal component analysis (SSM-PCA) method to identify and validate a metabolic pattern specific for CJD (2) determined the accuracy of the clinical diagnosis of parkinsonisms 12 months after imaging and compared it with the diagnosis calculated by an automatic logistic differential diagnostic algorithm based on 18F-FDG PET images which was considered gold standard (3) analyzed the difference in motor and cognitive brain metabolic patterns specific for PD in different stages of PD, compared it with other parkinsonian syndromes and evaluated its role in differential diagnosis. Results: (1.) CJDRP was identified and validated and its clinical significance was proven by significant correlations with patients’ clinical measures. It was found to be specific for CJD in contrast to AD and bvFTD. (2.) A comparison of real-life clinical diagnosis with automated diagnosis based on 18F-FDG PET as the gold standard showed 94.7% sensitivity, 83.3% specificity, 81.8% positive predictive value (PPV), and 95.2% negative predictive value (NPV) for PD and 88.2%, 76.9%, 71.4%, and 90.9% for APS diagnosis made by clinical neurologists. (3.) A consistent relationship between motor and cognitive patterns in PD patients was found. The delta, the difference between motor and cognitive PD patterns, steadily progressed with disease progression in several cross-sectional and longitudinal cohorts. Moreover, combination of motor pattern and the delta accurately discriminated PD patients from APS. Conclusion: In this research project, we provided a novel multivariate CJD specific brain pattern with potential use in basic neurodegenerative research. Further, superiority of 18F-FDG PET based diagnosis against clinical one has been demonstrated in real clinical practice and a study of metabolic brain patterns in PD associated with motor symptoms and cognition provided clues of disease/neurodegeneration progression consistent with the Braak hypothesis. To conclude, with this research, we provided novel insights into the pathophysiology of neurodegeneration in CJD, PD and APS and laid the foundation for the introduction of algorithm-based diagnosis established on the basis of multivariate brain patterns into clinical practice. Pathophysiological knowledge and accurate diagnosis are prerequisites for successful disease modifying trials in the future. The above-mentioned network analytical methods are increasingly being used in brain network research and in the clinical diagnosis of neurodegenerative diseases. This PhD thesis has contributed to the general knowledge of functional brain networks, an emerging scientific field, which is in detail reviewed in the last chapter of dissertation.

Objectives: Levodopa/carbidopa intrajejunal gel (LCIG) is an effective therapeutic strategy to overcome levodopa-induced motor complications in advanced Parkinson's disease (PD). However, it requires invasive percutaneous endoscopic gastrojejunostomy (PEG-J) and may be associated with serious adverse effects (AE). In this study, we aimed to evaluate long-term AEs related to LCIG treatment in a large homogenous cohort of advanced PD patients. Methods: One hundred three consecutive PD patients were regularly monitored for LCIG-related, PEG-J-related, and device-related AEs up to 14 years. Incidence of AEs was studied in time applying a time-to-event analysis and Cox proportional hazard model with age, disease duration, gender, and recurrent AE as covariates. Health-related quality of life (HRQoL) was estimated at each visit and compared to HRQoL before the LCIG treatment. Results: Among 296 AEs noted, 48.8% were LCIG-related, 32.4% PEG-J-related, and 19.6% device-related. While most of the studied AEs steadily accumulated throughout the follow-up period, 24.3% of the patients (95% CI 10.1%–36.3%) experienced PEG-J-related AE already within the first days after the PEG-J insertion. Cox model revealed that older patients had higher probability of psychosis, PEG-J- and device-related AEs (p < .05, p < .05, and p = .02) and suggested increased recurrence risk in those with early PEG-J and device-related AEs. Despite relatively high incidence of AEs, HRQoL significantly increased in the follow-up period (p < .0001). Conclusion: AEs related to LCIG treatment are common. Therefore, careful patient selection and monitoring throughout the treatment is recommended, especially in those with early side effects. Nevertheless, LCIG significantly improves HRQoL in advanced PD patients on a long term.

Diplomsko delo predstavlja tehnologijo prostozračne optične povezave. V zadnjem desetletju je bil svet priča ogromnemu povečanju prometa, prenesenega v telekomunikacijskih omrežjih. Na območjih, kjer je postavitev optičnih vlaken nemogoča oziroma predraga, je rešitev prostozračna optična povezava. Za namen diplomske naloge so najprej opisane lastnosti in področja uporabe prostozračnih optičnih zvez. Opisane so sprejemno – oddajne enote ter pregled dejavnikov, ki neposredno vplivajo na prenosno pot. Najbolj so izpostavljeni vremenski vplivi, saj ti največ vplivajo na kakovost prenosa. Opisan je svetlobni spekter v katerem delujejo prostozračne optične komunikacije, nato pa še poglavitna dela teh sistemov. To sta laserska dioda, ki oddaja v bližnjem infrardečem spektru ter fotodioda za sprejem signalov. Zadnji del naloge je namenjen praktičnemu preizkusu, s katerim sem želel predstaviti prostozračno optično zvezo. Z lasersko diodo prenašamo amplitudno moduliran zvok do sprejemne fotodiode. The following thesis is presenting a technology of the free space optics. In last decade the world has witnessed a huge increase of data traffic transferred in telecommunication networks. Free space optics is a solution in areas where is impossible to put optical fiber or the costs is too high. For the purpose of introductory part of this thesis is to describe features and areas of free space optics. FSO units are shown and described with their transmitters and receivers and a list of factors, which have a direct influence on a data transfer. Weather influences are in particular emphasized, because they mostly impact in the quality of data transfer. Next chapter describes infrared spectrum, in which free space optics operate, and then main parts of these system. These are laser diode for transmitting and photodiode for receiving signals. Practical experiment is covered in the last part of the thesis in which I wanted to present FSO communication. Laser diode transmits amplitude modulated sound to the receiving photodiode.

V pričujočem delu je predstavljena posodobitev merilnega mesta in programiranje aplikacije za avtomatizacijo meritev U-I karakteristike varistorja. Posodobljeno merilno mesto vključuje osebni računalnik in inštrument, ki je povezan nanj, ter nadomešča stari, analogni inštrument, kateri ni imel možnosti povezave z računalnikom. Projekt se je začel zaradi zahtev kupcev po bolj točnih in računalniško obdelanih meritvah in merilnih rezultatih ter zaradi boljše sledljivosti in analize preteklih rezultatov. Za programiranje aplikacije sem uporabil programsko opremo National Instruments Labview, za izvedbo meritev pa inštrument Keithley 2410 SourceMeter, ki je priključen na osebni računalnik in v celoti voden preko napisane aplikacije. V delu je opisan varistor, opis obstoječega merilnega sistema, predstavljen je novi merilni sistem, na kratko je opisana primerjava podatkovnega vodila po standardu RS-232 in IEEE-488 vodila (GPIB, General Purpose Interface Bus), načrtovanje programa, zahteve, programiranje in opis programa, potek izvedbe meritve, rešitve problemov in zaključek z možnimi posodobitvami. V poglavju o varistorju je opisana osnovna naloga varistorjev, različne izvedbe le teh in karakteristike. Poglavje o obstoječem merilnem sistemu vsebuje stari merilni postopek in razloge za zamenjavo z novejšim sistemom. Omenjene so tudi druge možnosti glede implementacije merilnega mesta in obrazloženo je, zakaj je izbrana rešitev najbolj optimalna izbira. Opis novega sistema je samostojno poglavje, v katerem je opisan merilni postopek, podatkovne povezave med računalnikom in inštrumentom in razlogi za izbiro le teh. Opis delovanja programa nam pove, kako je program sestavljen ter kakšni ukazi so potrebni za komunikacijo z inštrumentom. Načrtovanje, potek in zahteve za program so opisane v poglavju Potek načrtovanja in programiranja. Opisani so tudi primeri neuresničenih zahtev in obrazloženo je, zakaj je temu tako. V poglavju o programiranju teče beseda o programskem okolju Labview, komponentah in dodatnih programskih paketih, ki sem jih uporabil pri programiranju. V opisu programa je razloženo, kakšne metode so uporabljene za najboljši prikaz merilnih rezultatov, ter kakšna je struktura programskega projekta. Potek testiranja elementa zahteva svoje poglavje in opisuje vse številke in kode, ki se prenesejo iz podatkovne baze, ki so potrebne za izvedbo meritve in za obdelavo rezultatov. Opisani so stresni testi za varistorje, primerjava karakteristik in izračuni koeficientov. Pri programiranju sem naletel na težave. Rešitve težav so opisane v poglavju rešitve problemov. V poglavju, kjer je opisano izvajanje programa, je diagram poteka in opis celotnega postopka ter slikovni prikaz zaslonskih slik po korakih. Zaključek je namenjen pregledu celotnega stanja in pogledu v prihodnost ter morebitne možne posodobitve programa. In the following work an update of the measurment site and programming of the aplication for measurement automatization of UI varistor characteristics is presented. The updated measuring site includes a personal computer and the high voltage testing instrument and replaces the old analog instrument, which did not have the possibility for connecting to a computer. The project started because of the demands of customers for a more accurate and computer aided measurements and also to achieve better traceability and analysis of measured data. For aplication programming the software Labview (by National Instruments) and 2410 SourceMeter (by Keithley) were used. The sourceMeter is fully managed by the computer. In the thesis I have described the varistor element, current measuring system, the new measuring system, short description of RS-232 and IEEE-488 (GPIB, General Purpose Interface Bus) data buses, program planning, customer demands, program code writting and code description, problem solving and cocnlusion with possible fututre upgrades. Chapter about the varistor element containes a description of its basic operation, various versions of varistors and their charateristics. The chapter on the current measuring system contains the old measurement procedure and the reasons for replacement with a new system. There are other options regarding the implementation of the measuring point and I have explained why the chosen solution is the most optimal. Description of the new system is an independent chapter, which describes the measurement procedure, the data connection between the computer and the instrument and the reasons for choosing these. Description of the program tells us what the program consists of and commands needed to communicate with the instrument. The design, development course and requirements for the program are described in this chapter. It also describes examples of unfulfilled requirements and explains the reasons for them. In the chapter on programming, Labview programming environment is discussed and also components and additional software packages which I used in programming. In the description of the program I have explained methods used to present the measurement results and the structure of the software project. Testing procedure for individual elements under test requires a seperate chapter in which I have described all of the needed numbers and codes that are transferred from the database and are essential for performing the measurement and processing of the results. Stress tests for varistors are also described as well as their U-I characteristics comparison and coeffcient calulations. During the programming, I have encountered some problems. Troubleshooting of them is described in the chapter about problem solving. The next chapter contains the program flow chart and the description of measuring procedure and step by step graphical screenshots. Conclusion chapter is dedicated for review of overall project status and future plans to find any possbile updates for the program.

The influence of pressure pulsations on the cavitation-vortex dynamics in a Francis-turbine draft tube is presented. The experiment was performed on a model Francis turbine in which pressure pulsations on the draft-tube wall and the cavitation-vortex dynamics were acquired simultaneously. The cavitation-vortex dynamics was recorded using a visualization method. An experimental model was proposed in which the cavitation-vortex dynamics was predicted based on recorded pressure information at one point on the draft-tube wall. The performance of the model is, on average, very good. The prediction of the cavitation-vortex dynamics shows better results when the distance between the pressure sensor and the cavitation vortex is short. V prispevku je predstavljen vpliv tlačnih utripanj na dinamiko kavitacijskega vrtinca v sesalni cevi francisove turbine. Pri eksperimentalnem delu na modelu francisove turbine so bila hkrati merjena utripanja tlaka na steni sesalne cevi in dinamika kavitacijskega vrtinca. Dinamika kavitacijskega vrtinca je bila merjena z metodo vizualizacije. Predstavljena je metoda, s katero je mogoče napovedati dinamiko kavitacijskega vrtinca na podlagi izmerjenih tlačnih utripanj v eni točki na steni sesalne cevi. Uspešnost napovedi je bila v povprečju zelo dobra. Napoved dinamike kavitacijskega vrtinca je bila uspesnejsa v primerih, ko je bil kavitacijski vrtinec v blizini tlačnega zaznavala.