<p dir="ltr">Emission and absorption spectroscopy diagnostics are useful for providing non-invasive,<br>quantitative measurements of various gas properties in combustion environments, including<br>temperature and species concentrations. These measurements become even more useful<br>when they are applied with high spatial and temporal resolution. This dissertation describes<br>several ways that both emission and absorption diagnostics were advanced through leveraging<br>improvements in mid-IR camera and laser technology and through refining the use of existing<br>techniques.<br>A literature review is provided for both laser absorption and emission spectroscopy. Previous advancements in spatially resolved techniques are explained. The fundamental equations<br>of spectroscopic diagnostics are reviewed, starting from statistical mechanics.<br>A spectrally-resolved emission imaging diagnostic is presented. This diagnostic provided<br>1-dimensional measurements of gas temperature and relative mole fraction of CO₂ and HCl<br>in flames. An imaging spectrometer and a high-speed mid-infrared camera were used to<br>provide 1D measurements of CO₂and HCl emission spectra with a spectral resolution of<br>0.46 cm^-1 at rates up to 2 kHz. Measurements were acquired in HMX and AP-HTPB flames<br>burning in air at 1 atm. This diagnostic was applied to characterize how the path-integrated<br>gas temperature of HMX flames varies in time and with distance above the burning surface.<br>Additionally, Abel inversion with Tikhonov regularization was applied to determine the radial<br>distribution of temperature and relative concentration of CO₂ and HCl within the core of<br>AP-HTPB flames.<br>Next, a similar emission imaging diagnostic is presented which uses spectrally-resolved<br>measurements of emission spectra at visible wavelengths, unlike the mid-infrared measure-<br>ments in the rest of this dissertation. This diagnostic provided 1D temperature measure-<br>ments of aluminum oxide (AlO), an intermediate product of aluminum combustion. While<br>this author created the AlO diagnostic, these measurements were performed alongside a CO<br>absorption diagnostic used by a different researcher to compare the flame bath gas (via CO)<br>and the region immediately around aluminum particles (via AlO) when varying forms of<br>aluminum powder were used in a propellant. This comparison allows analysis of the burning regime of aluminum particles. Evidence was found that nano-aluminum particles burn in<br>the kinetically controlled combustion regime, while micron-aluminum particles burn in the<br>diffusion-controlled regime.<br>Multi-spectral emission imaging of hypergolic ignition of ammonia borane (AB) is then<br>presented. Three high-speed cameras with multiple optical filters were used to capture<br>infrared and visible wavelength videos of four individual species during AB ignition: BO,<br>BO₂, HBO₂, and the B-H stretch mode of AB were imaged. The ignition process was<br>observed to act in two steps: gas evolution and then propagation of a premixed flame. The<br>evolution of the species and flame front revealed that boranes may continue to complete<br>combustion to a further degree than other boron fuels. This author performed the infrared<br>camera imaging and also ran infrared spectrograph measurements to confirm which species<br>were viewed through the optical filters.<br>Next, a scanned-wavelength direct-absorption diagnostic for directly measuring NH₃ in<br>high-temperature combustion environments is presented. A quantum cascade laser (QCL)<br>was scanned at 5 kHz over multiple NH₃ transitions between 959.9 cm⁻¹ and 960.3 cm⁻¹ to<br>measure path-integrated NH₃ temperature and mole fraction. Many NH₃ transitions overlap<br>with high-temperature water lines at commonly used diagnostic frequencies, severely limiting<br>those diagnostics’ capabilities in water-rich, high-temperature environments that are typical<br>of combustion applications. The optical frequencies used in this diagnostic are insensitive<br>to water absorption and thus remedy this issue. This diagnostic was demonstrated within<br>the flame of ammonia borane. AB-based fuels were burned in ambient air and translated<br>vertically to effectively scan the measurement line-of-sight vertically through the flame. Ad-<br>ditionally, flames of these fuels were characterized at a stationary height in an opposed-flow<br>burner (OFB) under O₂ flow.<br>The final chapter presents scanned-wavelength direct-absorption measurements of path-<br>integrated temperature and CO mole fraction in opposed-flow diffusion flames of hydroxyl-<br>terminated polybutadiene (HTPB). HTPB strands were held in an opposed-flow burner<br>under an opposed flow of O2 or 50/50 O₂/N₂ to create quasi-steady and quasi-1D diffusion<br>flames above the fuel strand. The opposed-flow burner was translated vertically to effectively<br>scan the measurement line-of-sight vertically through the flame. A quantum-cascade laser (QCL) was scanned across the P(2,20), P(0,31), and P(3,14) absorption transitions in CO’s<br>fundamental vibration bands near 2008 cm⁻¹ at 10 kHz to determine the path-integrated<br>temperature and CO mole fraction. The laser beam was passed through sapphire rods<br>held close to the flame edge to bypass the flame boundary and provide a well defined path<br>length for mole fraction measurements. The measured profiles and fuel regression rates<br>were compared to predictions produced by a steady opposed-flow 1D diffusion flame model<br>produced by researchers at the Army Research Lab. The model was generated with chemical<br>kinetics mechanisms employing two different assumptions for the nascent gaseous product of<br>HTPB pyrolysis: C₄H₆ or C₂₀H₃₂. It was found that the C₂₀H₃₂ model produced temperature<br>and CO profiles along with regression rates that agreed more closely with the measured<br>results.<br></p>

Background: Alterations of hypothalamic–pituitary–adrenal (HPA) axis activity and serotonergic signaling are implicated in the pathogenesis of human obesity and may contribute to its metabolic and mental complications. The association of these systems has not been investigated in human obesity. Objective: To investigate the relation of HPA responsiveness and serotonin transporter (5-HTT) availability in otherwise healthy individuals with obesity class II or III (OB) compared to non-obesity controls (NO). Study participants: Twenty-eight OB (21 females; age 36.6 10.6 years; body mass index (BMI) 41.2 5.1 kg/m2) were compared to 12 healthy NO (8 females; age 35.8 7.4 years; BMI 22.4 2.3 kg/m2), matched for age and sex. Methods: HPA axis responsiveness was investigated using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test, and curve indicators were derived for cortisol and adrenocorticotropic hormone (ACTH). The 5-HTT selective tracer [11C]DASB was applied, and parametric images of the binding potentials (BPND) were calculated using the multilinear reference tissue model and evaluated by atlas-based volume of interest (VOI) analysis. The self-questionnaires of behavioral inhibition system/behavioral activation system (BIS/BAS) with subscales drive, fun-seeking and reward were assessed. Results: OB showed significant positive correlations of ACTH curve parameters with overall 5-HTT BPND (ACTHAUC: r = 0.39, p = 0.04) and 5-HTT BPND of the caudate nucleus (ACTHAUC: r = 0.54, p = 0.003). In NO, cortisol indicators correlated significantly with BPND in the hippocampus (cortisolAUC: r = 0.59, p = 0.04). In OB, BAS reward was inversely associated with the ACTHAUC (r = 0.49, p = 0.009). Conclusion: The present study supports a serotonergic-neuroendocrine association, which regionally differs between OB and NO. In OB, areas processing emotion and reward seem to be in-volved. The finding of a serotonergic HPA correlation may have implications for other diseases with dysregulated stress axis responsiveness, and for potential pharmacologic interven-tions.

Eine der drei Säulen der Krebsbehandlung ist die Strahlentherapie. Einer der neuesten Ansätze hierbei ist die Bestrahlung mit Ionen, zurzeit insbesondere Protonen und Kohlenstoffionen. Diese Hochpräzisionstherapie erfordert ein hohes Maß an Kontrolle, da die applizierte Dosisverteilung sehr empfindlich von Dichteveränderungen im durchstrahlten Gewebe abhängt. Das bisher einzige klinisch eingesetzte Verfahren zur in vivo Überwachung der Dosisapplikation bei Ionenbestrahlungen ist die Positronen-Emissions-Tomographie (PET). Sie ermöglicht eine Verifikation der Teilchenreichweite sowie der Lage des Bestrahlungsfeldes. Die mit der PET-Methode gemessene Aktivitätsverteilung lässt sich jedoch nicht direkt mit der geplanten Dosisverteilung vergleichen. Daher ist eine Vorherberechnung der erwarteten Aktivitätsverteilung auf der Grundlage des Bestrahlungsplanes notwendig, welche dann mit der Messung verglichen wird und eine qualitative Beurteilung der Bestrahlung ermöglicht. Die Vorherberechnung der erwarteten Aktivitätsverteilung erfordert bislang die Kenntnis einer Vielzahl von Wirkungsquerschnitten. Nur für wenige dieser Wirkungsquerschnitte liegen jedoch Messdaten im benötigten Energiebereich und mit ausreichender Genauigkeit vor. Daher verwenden viele Monte-Carlo-Simulationen intrinsische Kernmodelle oder semi-empirische Modellierungen, die häufig eine unzureichende Genauigkeit aufweisen. In Fachkreisen ist bisher noch nicht geklärt, welches die optimale Ionensorte für die Tumortherapie ist. Insbesondere Lithiumionen weisen aufgrund ihrer physikalischen und radiobiologischen Eigenschaften ein großes Potenzial auf. Auch für Bestrahlungen mit diesen Ionen ist ein PET-Monitoring der Therapie erstrebenswert. In der vorliegenden Arbeit wird zunächst die Anwendbarkeit der Reichweite-Verifikation mittels PET bei Bestrahlung mit Lithiumionen gezeigt. Des Weiteren wird ein Konzept zur Modellierung der Positronenemitter-Verteilung ohne Kenntnis der Wirkungsquerschnitte entwickelt. Diese Vorhersage beruht auf in Referenzmaterialien (Wasser, Graphit und Polyethylen) gemessenen tiefenabhängigen Positronenemitter-Yields, mit welchen durch geeignete Linearkombination die Verteilung der Positronenemitter in beliebigen Materialien bekannter Stöchiometrie vorausberechnet werden kann. Die Anwendbarkeit des Yield-Konzeptes wird gezeigt für Lithium- und Kohlenstoffbestrahlungen homogener Polymethylmethacrylat (PMMA) Targets sowie verschiedener inhomogener Targets. / One of the three main tumour treatment forms is radiation therapy. Here, the application of ion beams, in particular protons and carbon ions, is of growing importance. This high precision therapy requires a consequent monitoring of the dose delivery since the induced dose deposition is very sensitive to density changes in the irradiated tissue. Up to now, positron emission tomography (PET) is the only in vivo method in clinical use for monitoring the dose deposition in ion beam therapy. It allows for the verification of the particle range as well as the position of the irradiation field. The distribution of activity measured by means of PET cannot be compared directly to the planned dose distribution. Thus, a calculation of the expected activity distribution is required which then can be compared to the measurement. Simulation of the expected activity distribution requires the exact knowledge of various cross sections. Only a few of them have been measured in the required energy range so far. Therefore, in Monte Carlo simulations often intrinsic nuclear models or semi-empirical parametrization are used which often exhibit insufficient accuray. Among experts the question on the optimum ion species for tumour therapy is still open. Especially lithium ions exhibit a great potential due to their favourable physical and radiobiological properties. Also for these ions a PET monitoring is highly desirable. The presented work shows the feasibility of range verification by means of PET for lithium irradiation. Furthermore, a concept for modeling positron emitter distributions without the knowledge of cross sections is developed. This prediction is based on depth-dependent positron emitter yields measured in reference materials (water, graphite and polyethylene). With these data the positron emitter distribution in any material of known stoichiometry can be calculated by means of an appropriate linear combination. The feasibility of the yield concept is shown for lithium and carbon irradiation, respectively, of homogeneous polymethyl methacrylate (PMMA) as well as various inhomogeneous targets.

Eine der drei Säulen der Krebsbehandlung ist die Strahlentherapie. Einer der neuesten Ansätze hierbei ist die Bestrahlung mit Ionen, zurzeit insbesondere Protonen und Kohlenstoffionen. Diese Hochpräzisionstherapie erfordert ein hohes Maß an Kontrolle, da die applizierte Dosisverteilung sehr empfindlich von Dichteveränderungen im durchstrahlten Gewebe abhängt. Das bisher einzige klinisch eingesetzte Verfahren zur in vivo Überwachung der Dosisapplikation bei Ionenbestrahlungen ist die Positronen-Emissions-Tomographie (PET). Sie ermöglicht eine Verifikation der Teilchenreichweite sowie der Lage des Bestrahlungsfeldes. Die mit der PET-Methode gemessene Aktivitätsverteilung lässt sich jedoch nicht direkt mit der geplanten Dosisverteilung vergleichen. Daher ist eine Vorherberechnung der erwarteten Aktivitätsverteilung auf der Grundlage des Bestrahlungsplanes notwendig, welche dann mit der Messung verglichen wird und eine qualitative Beurteilung der Bestrahlung ermöglicht. Die Vorherberechnung der erwarteten Aktivitätsverteilung erfordert bislang die Kenntnis einer Vielzahl von Wirkungsquerschnitten. Nur für wenige dieser Wirkungsquerschnitte liegen jedoch Messdaten im benötigten Energiebereich und mit ausreichender Genauigkeit vor. Daher verwenden viele Monte-Carlo-Simulationen intrinsische Kernmodelle oder semi-empirische Modellierungen, die häufig eine unzureichende Genauigkeit aufweisen. In Fachkreisen ist bisher noch nicht geklärt, welches die optimale Ionensorte für die Tumortherapie ist. Insbesondere Lithiumionen weisen aufgrund ihrer physikalischen und radiobiologischen Eigenschaften ein großes Potenzial auf. Auch für Bestrahlungen mit diesen Ionen ist ein PET-Monitoring der Therapie erstrebenswert. In der vorliegenden Arbeit wird zunächst die Anwendbarkeit der Reichweite-Verifikation mittels PET bei Bestrahlung mit Lithiumionen gezeigt. Des Weiteren wird ein Konzept zur Modellierung der Positronenemitter-Verteilung ohne Kenntnis der Wirkungsquerschnitte entwickelt. Diese Vorhersage beruht auf in Referenzmaterialien (Wasser, Graphit und Polyethylen) gemessenen tiefenabhängigen Positronenemitter-Yields, mit welchen durch geeignete Linearkombination die Verteilung der Positronenemitter in beliebigen Materialien bekannter Stöchiometrie vorausberechnet werden kann. Die Anwendbarkeit des Yield-Konzeptes wird gezeigt für Lithium- und Kohlenstoffbestrahlungen homogener Polymethylmethacrylat (PMMA) Targets sowie verschiedener inhomogener Targets. / One of the three main tumour treatment forms is radiation therapy. Here, the application of ion beams, in particular protons and carbon ions, is of growing importance. This high precision therapy requires a consequent monitoring of the dose delivery since the induced dose deposition is very sensitive to density changes in the irradiated tissue. Up to now, positron emission tomography (PET) is the only in vivo method in clinical use for monitoring the dose deposition in ion beam therapy. It allows for the verification of the particle range as well as the position of the irradiation field. The distribution of activity measured by means of PET cannot be compared directly to the planned dose distribution. Thus, a calculation of the expected activity distribution is required which then can be compared to the measurement. Simulation of the expected activity distribution requires the exact knowledge of various cross sections. Only a few of them have been measured in the required energy range so far. Therefore, in Monte Carlo simulations often intrinsic nuclear models or semi-empirical parametrization are used which often exhibit insufficient accuray. Among experts the question on the optimum ion species for tumour therapy is still open. Especially lithium ions exhibit a great potential due to their favourable physical and radiobiological properties. Also for these ions a PET monitoring is highly desirable. The presented work shows the feasibility of range verification by means of PET for lithium irradiation. Furthermore, a concept for modeling positron emitter distributions without the knowledge of cross sections is developed. This prediction is based on depth-dependent positron emitter yields measured in reference materials (water, graphite and polyethylene). With these data the positron emitter distribution in any material of known stoichiometry can be calculated by means of an appropriate linear combination. The feasibility of the yield concept is shown for lithium and carbon irradiation, respectively, of homogeneous polymethyl methacrylate (PMMA) as well as various inhomogeneous targets.

Résumé : Les personnes atteintes de la maladie d’Alzheimer présentent une diminution de la capture cérébrale du glucose, qui semble être impliquée dans le développement des problèmes cognitifs associés à la maladie. Toutefois, il n’y a encore aucun consensus quant à savoir si la capture cérébrale du glucose est diminuée chez les personnes âgées cognitivement saines. En condition de déficit de glucose, les cétones sont le substrat énergétique alternatif pour le cerveau. La diète cétogène, induisant une cétose légère, améliore les fonctions cognitives chez les modèles animaux et chez l’homme. Notre premier objectif était d’évaluer l’effet du vieillissement sain et de la diète cétogène sur la capture cérébrale du glucose et des cétones chez le rat. Pour cela, la capture cérébrale de radiotraceurs analogues au glucose et aux cétones a été mesurée par tomographie par émission de positons. Nos résultats montrent que la capture des deux principaux substrats énergétiques du cerveau est globalement similaire chez des rats sains jeunes et âgés, mais est plus élevée suite à la diète cétogène. L’induction d’une cétose légère pourrait corriger la diminution de capture cérébrale du glucose subvenant au cours de la maladie d’Alzheimer. Le second objectif était de déterminer l’effet d’une diète cétogène sur le métabolisme cérébral du glucose et des cétones chez le rat. Pour cela, les différents intermédiaires des voies métaboliques du glucose et des cétones ont été mesurés par spectroscopie par résonance magnétique nucléaire. Les résultats démontrent que le métabolisme du glucose et des cétones dans les cellules du cerveau est plus élevé suite à la diète cétogène. Le contenu en acide [gamma]-aminobutyrique, le principal neurotransmetteur inhibiteur, est aussi plus élevé suite à la diète cétogène, ce qui pourrait contribuer à l’effet antiépileptique de la diète cétogène. Le troisième objectif était d’évaluer l’impact d’une restriction calorique à long terme, pouvant induire une cétose légère, sur le métabolisme cérébral chez des rats âgés sains. Nos résultats montrent que, couplée à une diète à haute teneur en sucrose et faible en acides gras oméga-3, la restriction calorique à long terme chez les rats âgés ne modifie pas le profil des métabolites et des acides gras du cerveau. La déficience en acides gras oméga-3 et la surcharge de sucrose pourraient empêcher une grande partie des effets bénéfiques de la restriction calorique au cerveau.//Abstract : Alzheimer’s disease is associated with a reduction of brain glucose uptake, which may be involved in the development of the cognitive problems associated with the disease. It is however unclear whether brain glucose uptake is decreased in the cognitively healthy elderly. Under conditions of glucose deficit, ketones are the alternative brain energy substrate. A mild ketosis, induced by the ketogenic diet, improves cognitive functions in animal models and humans. Our first objective was to evaluate the effect of healthy aging and of a ketogenic diet on brain glucose and ketone uptake in the rat. Brain uptake of radiotracers analogous to glucose and ketones was measured by positron emission tomography. Our results show that the uptake of the brains two main energy substrates is generally similar in healthy young and aged rats, but is higher under the ketogenic diet. The induction of a mild ketosis may compensate the reduction of brain glucose uptake occurring in Alzheimer’s disease. The second objective was to assess the effect of a ketogenic diet on brain glucose and ketone metabolism in the rat. Metabolic pathway intermediates of glucose and ketones were measured by nuclear magnetic resonance spectroscopy. Results show that glucose and ketone metabolism in brain cells is higher under the ketogenic diet. Content of [gamma]-aminobutyric acid, the main inhibitory neurotransmitter, is also higher under the ketogenic diet, which could contribute to the antiepileptic effect of the ketogenic diet. The third objective was to evaluate the effect of a long-term calorie restriction, which may induce a mild ketosis, on brain metabolism in healthy aged rats. Our results show that, in conjunction with a diet enriched in sucrose and low in omega-3 fatty acids, long-term calorie restriction in aged rats does not change brain metabolite and fatty acid profiles. Omega-3 fatty acid deficiency and an overload of sucrose may prevent the beneficial effects associated with calorie restriction in the brain.

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Bone is a remarkable multifunctional tissue with the ability to regenerate and remodel without generating any scar tissue. However, bone loss due to injury or diseases can be a great challenge and affect the patient significantly. Autologous bone grafting is commonly used throughout the world. Autograft both fills the void and is bone inductive, housing the particular cells that are needed for bone regeneration. However, a regenerative complement to autograft is of great interest as the use of biomaterials loaded with bioactive molecules can avoid donor site morbidity and the problem of a limited volume of material. Two such regenerative products that utilise bone morphogenetic protein (BMP)-7 and -2 have been used for more than a decade clinically. Unfortunately, several side effects have been reported, such as severe swelling due to inflammation and ectopic bone formation. Additionally, the products require open surgery and use of supra physiological doses of the BMPs due to poor localisation and retention of the growth factor. The purpose of this thesis was to harness the strong inductive capacity of the BMP-2 by optimising the carrier of this bioactive protein, thereby minimising the side effects that are associated with the clinical products and facilitating safe and localised bone regeneration. We focused on an injectable hyaluronan-based carrier developed through polymer chemistry at the University of Uppsala. The strategy was to use the body’s own regenerative pathway to stimulate and enhance bone healing in a manner similar to the natural bone-healing process. The hyaluronan-based carrier has a similar composition to the natural extracellular matrix and is degraded by resident enzymes. Earlier studies have shown improved properties when adding hydroxyapatite, a calcium phosphate that constitutes the inorganic part of the bone matrix. In Paper I, the aim was to improve the carrier by adding other forms of calcium phosphate. The results indicated that bone formation was enhanced when using nano-sized hydroxyapatite. In Paper II, we discovered the importance of crushing the material, thus enhancing permeability and enlarging the surface area. We wished to further develop the carrier system, but were lacking an animal model with relatively high throughput, facilitated access, paired data, and we were also committed to the 3Rs of refinement, reduction, and replacement. To meet these challenges, we developed and refined an animal model, and this is described in Paper III. In Paper IV, we sought to further optimise the biomaterial properties of the hydrogel through covalent bonding of bisphosphonates to the hyaluronan hydrogel. This resulted in exceptional retention of the growth factor BMP-2. In Paper V, SPECT/PET/µCT was combined as a tri-modal imaging method to allow visualisation of the biomaterial’s in situ action, in terms of drug retention, osteoblast activity and mineralisation. Finally, in Paper VI the correlation between existing in vitro results with in vivo outcomes was observed for an array of biomaterials. The study identified a surprisingly poor correlation between in vitro and in vivo assessment of biomaterials for osteogenesis.

L’objectif général de ce travail de thèse a été de caractériser in vivo, chez l’Homme, les réorganisations mnésiques retrouvées dans l’épilepsie temporo-mésiale pharmaco-résistante.Nous nous sommes appuyés sur une approche multimodale d’imagerie combinant étude de la connectivité et des réseaux d’activations mnésiques en IRMf, et étude de la consommation métabolique régionale inter-critique de glucose en TEP. Il s’agissait, notamment, de mieux comprendre la relative préservation mnésique retrouvée chez certains de ces patients, malgré l’implication du cortex temporal interne au sein de leurs réseaux épileptiques.Nos résultats, obtenus pour l’encodage d’items uniques non matériel-spécifiques, apportent des connaissances nouvelles sur l’adaptation fonctionnelle des réseaux cognitifs au sein et en dehors de la zone épileptogène, expliquant les différences de performance mnésique en reconnaissance, et leur lien possible avec les réseaux épileptiques.Ces travaux suggèrent, notamment, l’existence de ressources fonctionnelles additionnelles efficaces, à la fois locales et à distance, impliquant la voie visuelle ventrale bilatérale. Ces processus de compensation pourraient être conditionnés par les caractéristiques propres de l’atteinte primitive, et en particulier une implication différente des structures temporales internes au sein de la zone épileptogène. L’altération fonctionnelle de ce système perceptivo-mnésique pourrait induire une réorganisation inefficace plus large, sollicitant l’activation alternative des réseaux de l’attention, au niveau des régions fronto-cingulaires et pariétales. / The overall objective of this thesis was to characterize in vivo the human memory reorganization observed in medial temporal lobe epilepsy, in particular for recognition memory.We conducted a multimodal neuroimaging approach, combining the study of connectivity and memory activation networks with fMRI, and the study of inter-ictal cerebral metabolic rate of glucose with PET. We aimed to better understand the relative preservation of memory found in some patients, despite the involvement of the medial temporal lobe within their epileptic networks. Our findings, obtained for the encoding of non material-specific single items, provide new insights into the functional adaptation of cognitive networks, within and outside the epileptogenic zone, and help to explain the differences in recognition performance, and their possible relationship with epileptic networks. These studies suggest, in particular, the existence of local and remote compensatory mechanisms which are functionally effective and involve the ventral visual stream bilaterally. These could be influenced by the exact involvement of medial temporal structures within the epileptogenic zone. The impairment of this perceptive-memory system may lead to a more large-scale reorganization with the alternative activation of an inefficient network of attention-related areas involving fronto-cingulate and parietal cortices.

<p>Studija je imala za cilj da pokaže značaj primene PET/CT pregleda u planiranju radiolo&scaron;ke terapije kod pacijenata obolelih od Hočkinovog linfoma. U Vojvodini je 2009. godine prema podacima Registra za maligne neoplazme Vojvodine incidence za Hočkinov limfom iznosila 2,7 na 100 000 dok je mortalitet bio 1,1 na 100 000 stanovnika. Na osnovu dostupnih podataka Registra za maligne neoplazme Vojvodine beleži se porast incidence u protekloj deceniji. Procenat obolelih u Vojvodini u korelaciji je sa podacima koje navodi i Međunarodna agencija za istraživanje raka iz Liona (IARC). U Evropi i u Sjedinjenim Američkim Državama postoji bimodularna kriva incidence po starosti koja pokazuje maksimalne vrednosti u period između 20 i 30 godina i nakon 55. godine. S obzirom da od Hočkinovog limfoma dominantnije obolevaju mlađe osobe a da bolest ima dobru prognozu neophodno je iznaći nove načine za inicijalno određivanje stadijuma bolesti, kao i metode koje mogu da unaprede kvalitet lečenja. Jedan od načina je primena &scaron;to savremenijih dijagnostičkih metoda. PET-CT je imidžing metoda koja poslednjih godina zauzima značajno mesto u određivanju stadijuma malignih bolesti kao i u proceni odgovora na primenjenu terapiju. Fuzionisanjem skenova PET-a i CT-a dobija se PET-CT slika koja prikazuje funkcionalno stanje pojedinih tkiva i organa (PET) sa anatomskim detaljima (CT). Cilj istraživanja je bio da se utvrdi prednost PET-CT pregleda u planiranju radioterapije kod pacijenata sa supradijafragmalnom lokalizacijom bolesti. Nakon postavljanja dijagnoze Hočkinovog limfoma kod pacijenata je urađen PET-CT i planiranje radiolo&scaron;ke terapije. Zračna terapija je planirana na osnovu nalaza PET-CT-a i njegovom fuzijom sa CT-om za planiranje radiolo&scaron;kog lečenja. Dobijeni planovi su poređeni sa onim koji su rađeni standardnom 3D konformalnom tehnikom bez fuzije. Poređeni su klinički volumeni (CTV) i planirani volumen (PTV) kao i razlike u njihovoj obuhvaćenosti preskribovanom dozom. Pokazano je da postoji statistički značajna razlika u ciljnim volumenima kao i u njihovoj obuhvaćenosti. Posmatrani su takođe i rizični organi- srce, pluća, dojke, &scaron;titasta žlezda, kičmena moždina i doze koje oni prime. Dokazano je da su sa statističkom značajno&scaron;ću dozna opterećenja na navedene rizične organe manja kada se planiranje vr&scaron;i na osnovu fuzije sa PET-CT-om, te se na osnovu toga može reći da će i očekivane manifestacije kasne toksičnosti biti manje. Istraživanjem je potvrđena hipoteza da PET/CT ima veliku prednost u planiranju radioterapije jer smanjuje zapremine ciljnih volumena i doprinosi pobolj&scaron;anju kvaliteta radiolo&scaron;kog lečenja.</p> / <p>This study aimed to prove that the use of PET/CT in radiotherapy planning makes a material change in the course of the treatment of the patients with Hodgkin&#39;s lymphoma. According to the data from the Registry of malignant neoplasms in Vojvodina, incidence of Hodgkin&#39;s lymphoma in Vojvodina in 2009 was 2.7 per 100 000, while the mortality rate was 1.1 per 100 000 inhabitants. Based on the available data, the said Register recorded an increase in the incidence over the past decade. The percentage of patients who were registered in Vojvodina is in correlation with the data cited by the International Agency for Research on Cancer in Lyon (IARC).In Europe and in the United States the disease has a bi-modular distribution distribution with the highest frequency rate in persons ageing from 20-30 years and people older than 55 years. Due to the fact that the dominant Hodgkin&#39;s lymphoma affects young people and having in mind the good prognosis of the disease, it is necessary to find a new modality for the initial staging of disease and methods which can improve the quality of treatment. PET/CT is the imaging method which has in recent years had an important role in the staging of malignancies, as well in the evaluation of response to therapy. PET/CT image is obtained by fusing PET scans with CT and it show functional status of certain tissues and organs (PET) with anatomical details (CT).The object of this study was to show that PET/CT examinations are preferred imaging method in radiotherapy planning in patients with localized disease above the diaphragm. After they had been diagnosed with HL, patients underwent PET/CT scan which was later used for delineation in radiotherapy planning. In this study, radiation therapy was planned on the basis of the findings of PET /CT and its fusion with CT for planning radiological treatment. The resulting plans were compared with those made using standard 3D conformal technique without fusion. Clinical volume (CTV) and the planned volume (PTV) and the differences in their coverage with the prescription dose in both plans were also compared. The study has shown a statistically significant difference in the target volume and their coverage. In addition, the dose which receive organs at risk was also examined. It has been shown that organs at risk were exposed to lower doses when using PET/CT fusion in radiotherapy planning and consequently, less incidence of late toxicity is to be expected. The study confirmed the hypothesis that PET /CT has a great advantage in the planning of radiotherapy because it reduces the volume of the target volume and improves the quality of radiation treatment.</p>

Résumé : Le trouble de l’acquisition de la coordination (TAC), d’étiologie encore indéterminée, est une anomalie neurologique affectant environ 6% des enfants de l'âge scolaire. Le TAC se manifeste essentiellement par un déficit au niveau des exécutions motrices. Le présent travail de recherche comporte deux volets portant sur le TAC. Premièrement, une étude clinique sur 129 sujets âgés de 4 à 18 ans a permis de classifier les caractéristiques du TAC en sous-groupes cliniques. Trente-trois caractéristiques du TAC, les plus fréquemment rapportées dans la littérature, ont été recensées chez nos sujets. L'application d'évaluations statistiques a permis de faire ressortir trois classes essentielles. Le deuxième volet consistait à identifier les régions cérébrales impliquées dans une tâche motrice à l'aide de l'imagerie par la tomographie d'émission par positrons (TEP). Deux sujets avec TAC et deux sujets normaux ont été étudiés en deux séances d'imagerie TEP dont l'une au repos et l'autre en tapotant du pouce sur les doigts de la main gauche non-dominante. Les analyses du premier volet ont montré, entre autres, que le TAC touchait 3.17 garçons pour une fille, que tous les sujets étaient lents, que 47% des sujets étaient gauchers ou ambidextres alors que seulement 10% sont gauchers dans la population générale, que 26% avaient une dyspraxie verbale, et que 83% avaient été diagnostiqués anxieux. Les sujets ont été classés en trois sous-groupes: 1- maladroits et autres caractéristiques, sans problème de langage; 2- trouble de l’estime de soi et relation avec les pairs; 3- difficulté de langage. En imagerie, les structures cérébrales ont été classées selon leur captation du 18F-fluorodesoxyglucose (FDG) dans les hémisphères droit et gauche, avant et après l'activation, et en comparaison avec les sujets normaux. Trois types de structures cérébrales sont ressortis avec les statistiques: des structures activées, celles relativement non sollicitées et des structures désactivées. Il y avait plus de variations dans la captation du FDG chez les sujets avec TAC que chez les normaux. En conclusion, la caractérisation des sujets avec TAC par le diagnostic clinique et par l'imagerie peut procurer un plan de thérapie adéquat et ciblé étant donné que le TAC a un large spectre et pourrait coexister avec d'autres déficits cérébraux. / Abstract : Developmental Coordination Disorder (DCD) is a neurological abnormality affecting approximately 6% of children of school age. DCD is essentially manifested by deficit in motor executions. The present research aims two parts of DCD. First, a clinical study on 129 subjects aged 4 to 18 years old allowed to classify DCD characteristics (subtyping) in three classes. Thirty-three features of DCD, the most frequently reported in literature, have been identified in our subjects. The application of statistical clustering produced three essential classes. The second part was to identify the brain regions involved in a motor task using positron emission tomography (PET) imaging. Subjects with DCD and control subjects were studied in two PET imaging sessions at rest and then by tapping the thumb on each finger of the left non-dominant hand. The results showed, that DCD concerned 3.17 boys for one girl, all subjects were slow, 47% of the subjects were left-handed or ambidextrous while only 10% are left-handed in general population, 26% had a verbal dyspraxia, and 83% had been diagnosed with anxiety. Subjects were classified into three groups: 1- clumsy and other features without language problem; 2- self-esteem and peer relationships concern; 3- difficulty of spoken language. With PET imaging, the brain structures were classified according to their uptake of 18F-fluorodeoxyglucose (FDG) in the right and left hemispheres before and after activation, and compared with normal subjects. Three types of brain structures statistically emerged: activated structures, those relatively unsolicited and those disabled. There was more variation in uptake of FDG in patients with DCD than in control subjects. In conclusion, the characterization of subjects with DCD for clinical diagnostic and imaging can provide adequate and focused treatment plan since DCD has a broad spectrum and could coexist with other brain deficits.