A epilepsia do lobo temporal (ELT) é a forma mais comum de epilepsia e a mais resistente ao tratamento medicamentoso. Existem diversos tipos de drogas anti-epilépticas usadas no controle das crises. Entretanto, em alguns casos, esse tipo de tratamento não é eficaz e a cirurgia para remoção da zona epileptogênica (ZE) pode ser uma alternativa recomendada. A ZE é definida como aquela onde as crises são originadas. Trata-se de um conceito teórico e, atualmente, não existem técnicas capazes de delimitá-la precisamente. Na prática, exames de EEG, vídeo-EEG, MEG, SPECT, PET e diversas técnicas de MRI, em especial as funcionais, têm sido usados para mapear zonas relacionadas à ZE. Contudo, em alguns casos, os resultados permanecem não convergentes e a determinação da ZE inconclusiva. Desse modo, é evidente a importância do surgimento de novas metodologias para auxiliar a localização da ZE. Assim, pois, o objetivo deste trabalho foi desenvolver dois métodos para a avaliação da ZE, ambos baseados na imagem funcional por ressonância magnética. No primeiro, investigamos possíveis alterações da resposta hemodinâmica (HRF) quando da modulação da pressão parcial de CO2. Para tanto, fizemos um estudo sobre 22 pacientes com ELT e 10 voluntários assintomáticos modulando a pressão parcial de CO2 sanguíneo cerebral por um protocolo de manobra de pausa respiratória e outro de inalação passiva de CO2/ar. Os resultados mostram que o tempo de onset da HRF tende a ser maior e a amplitude da HRF tende a ser menor em áreas do lobo temporal de pacientes com ELT quando comparados com os dados de voluntários assintomáticos. Além disso, os resultados mostram mapas de onset individuais coincidentes com exames de SPECT ictal. O segundo estudo foi baseado em medidas de EEG-fMRI simultâneo. Neste, avaliamos a relação entres as potências dos ritmos cerebrais alfa e teta (EEG) e o contraste BOLD (fMRI) de 41 pacientes com ELT e 7 voluntários assintomáticos em estado de repouso. A análise da banda alfa mostrou correlações negativas nos lobos occipital, parietal e frontal tanto nos voluntários quanto nos pacientes com ELT. As correlações positivas nos voluntários foram dispersas e variáveis em ambos hemisférios cerebrais. Por outro lado, encontramos forte correlação positiva no tálamo e ínsula dos pacientes com ELT. Na análise da banda teta observamos correlações positivas bilaterais nos giros pré e pós central de voluntários. Ainda, foram observados clusters no cíngulo anterior, tálamo, ínsula, putamen, em regiões parietais superior, frontais e giros temporais. Também, utilizamos um cálculo de índice de lateralização (IL) no lobo temporal em confrontos entre pacientes com ELT à direita, pacientes com ELT à esquerda e voluntários assintomáticos. Verificamos que os ILs, utilizando os clusters obtidos nas análises em teta, foram coincidentes com o diagnóstico clínico prévio da localização da ZE em todas as análises dos grupos de pacientes com ELT à direita, e na maioria do grupo de pacientes com ELT à esquerda. De forma geral, verificamos que o método de hipercapnia se mostrou ferramenta interessante na localização da ZE comprovada pelos coincidentes achados pela avaliação de SPECT. Inferimos que o maior tempo de onset e menor amplitude da HRF observadas nos pacientes em relação a voluntários possam estar relacionados a um stress vascular devido à recorrência de crises. Já o método de ritmicidade alfa e teta proposto parece promissor para ser usado na determinação da lateralização da ZE em pacientes com ELT. / Temporal lobe epilepsy (TLE) is the most common and resistant form of epilepsy to anti-epileptic drug. There are several types of anti-epileptic drugs used in seizure control. However, in some cases drug treatment is not effective and surgery to remove the epileptogenic zone (EZ) is a recommended alternative. EZ is a theoretical concept and there are many techniques that have been applied to enclose it precisely. In practice, EEG, video-EEG, MEG, SPECT, PET and various MRI techniques, especially functional MRI (fMRI), have been used to map areas related to EZ. However, in some cases, the results remain non-convergent and the EZ, undefined. Therefore, the use of new methodologies to assist the location of EZ have been proposed. Herein, our goal was to develop two methods for assessing the EZ. The first one was designed to access changes in the hemodynamic response (HRF) of the EZ in response to hypercapnia. 22 patients with TLE and 10 normal volunteers were evaluated by modulating the partial pressure of CO2 during the acquisition of fMRI in a breathing holding and a passive inhalation CO2/air protocols. The results show increased onset times and decreased amplitude of the HRF in the temporal lobe of TLE patients compared with asymptomatic volunteers. Moreover, most patients had onset maps coincident with ictal SPECT localizations. The second proposed study was based on simultaneous EEG-fMRI acquisitions. The relationship between powers of alpha and theta bands (EEG) and BOLD contrast (fMRI) was investigated in 41 TLE patients and 7 healthy controls. Alpha band results show a consistent negative correlation in the occipital, parietal and frontal lobes both in controls and TLE patients. In addition, controls show disperse positive correlations in both hemispheres. On the other hand, TLE patients presented strong positive correlations in the thalamus and insula. Theta band analysis, in controls, primarily show positive correlations in bilateral pre-and post-central gyri. In patients, robust positive correlations were observed in the anterior cingulate gyrus, thalamus, insula, putamen, superior parietal, frontal and temporal gyri. Moreover, the lateralization index (LI) indicates a coincidence between the side of the EZ evaluated by clinical diagnosis and clusters detected in the theta band. In conclusion, the hipercapnia study showed to be an interesting tool in locating EZ and the results are similar to SPECT findings. The longer onset and lower amplitude of the HRF observed in patients may be related to a vascular stress due to the recurrence of seizures. Furthermore, alpha and theta rhythms may be a promising tool to be used in determining the lateralization of EZ in patients with TLE.

Sexually selected traits may also be subject to non-sexual selection. If optimal trait values depend on environmental conditions, then “narrow sense” (i.e., non-sexual) natural selection can lead to local adaptation, with fitness in a certain environment being highest among individuals selected under that environment. Such adaptation can, in turn, drive ecological speciation via sexual selection. To date, most research on the effect of narrow-sense natural selection on sexually selected traits has focused on precopulatory measures like mating success. However, postcopulatory traits, such as sperm function, can also be under non-sexual selection, and have the potential to contribute to population divergence between different environments. Here, we investigate the effects of narrow-sense natural selection on male postcopulatory success in Drosophila melanogaster. We chose two extreme environments, low oxygen (10%, hypoxic) or high CO₂ (5%, hypercapnic) to detect small effects. We measured the sperm defensive (P1) and offensive (P2) capabilities of selected and control males in the corresponding selection environment and under control conditions. Overall, selection under hypoxia decreased both P1 and P2, while selection under hypercapnia had no effect. Surprisingly, P1 for both selected and control males was higher under both ambient hypoxia and ambient hypercapnia, compared to control conditions, while P2 was lower under hypoxia. We found limited evidence for local adaptation: the positive environmental effect of hypoxia on P1 was greater in hypoxia-selected males than in controls. We discuss the implications of our findings for the evolution of postcopulatory traits in response to non-sexual and sexual selection.

A intolerância ao exercício físico na insuficiência cardíaca (IC) está relacionada a alterações hemodinâmicas e neurohumorais pela complexa interação dos reflexos cardiovasculares. Os quimiorreflexos central e periférico e o ergorreflexo estão envolvidos na hiperventilação de repouso e durante o exercício, contribuindo para intolerância ao esforço. Os objetivos do estudo foram avaliar o efeito da terapêutica com beta-bloqueador (betab) na resposta dos quimiorreflexos central e periférico e do ergorreflexo por meio das alterações da resposta ventilatória durante o teste de caminhada de seis minutos (T6M); e avaliar o efeito da sua otimização também sobre as catecolaminas plasmáticas e peptídeo natriurético do tipo B (BNP). Foram estudados 15 pacientes masculinos, 49.5 ± 2.5 anos, com diagnóstico de IC há mais de 3 meses, sem histórico de tratamento com betab, com fração de ejeção (FEVE) 25.9 ± 2.5%, classe funcional I-III (NYHA). Estes pacientes poderiam estar em uso de inibidores da enzima conversora da angiotensina, bloqueadores do receptor da angiotensina II e antagonista do receptor da aldosterona. Todos os indivíduos realizaram testes: ergoespirométrico em esteira segundo o protocolo de Naughton, três T6M em esteira com controle de velocidade pelo paciente randomizados (um com sensibilização dos quimiorreceptores centrais, um com sensibilização dos quimiorreceptores periféricos e um controle em ar ambiente - AA). Também realizaram T6M com e sem oclusão circulatória regional em membro inferior. Em relação aos exames laboratoriais, foram feitas análises de catecolaminas plasmáticas em repouso e BNP. Os pacientes foram então submetidos a tratamento medicamentoso padrão da Instituição, com introdução e otimização da terapêutica com ßb e, após seis meses, foram reavaliados. Após otimização do betab, houve melhora significativa na FEVE, de 26 ± 2,5 para 33 ± 2,6 (p < 0,05); diminuição de níveis de BNP (775 ± 163 para 257 ± 75; p < 0,01) e de catecolaminas plasmáticas (598 ± 104 para 343 ± 40; p < 0,05). Foi também observada diminuição significativa na frequência cardíaca de repouso, de 95.6 ± 4.5 para 69.0 ± 1.6 (p < 0,01), e aumento do pulso de O2 de repouso (3.7 ± 0.3 para 4.4 ± 0.3; p < 0,01) pós betab. Em relação ao pico do esforço, houve diminuição significativa da frequência cardíaca, de pico 144.0 ± 4.6 para 129.5 ± 4.2 (p < 0,05), aumento do pulso de O2 (11.9 ± 1.1 para 15.5 ± 0.8; p < 0,01), diminuição do VE/VCO2 slope 29.4(25.8-36.2) para 24.6 (22.5-27.5); p=0,03) e aumento do tempo de exercício (12.3 ± 1.3 para 16.1 ± 1.2; p=0,01), sem, entretanto, aumento do consumo de oxigênio. Houve diferença significativa em relação à distância percorrida no T6M entre os dois momentos (pré e pós) em todas as análises, tanto controle (AA) quanto para a sensibilização dos quimiorreceptores centrais e periféricos, além de diminuição da resposta ventilatória nas sensibilizações dos quimiorreflexos quando comparados com o controle. A otimização da terapêutica medicamentosa na IC, especialmente com betab, promove melhora hemodinâmica, metabólica e neurohormonal. O presente estudo, que examinou os efeitos da terapêutica com betab na resposta dos quimiorreflexos e ergorreflexo em pacientes com IC, documentou que o betab diminui a resposta dos quimiorreflexos durante o exercício em hipóxia e hipercapnia sem, entretanto, alterar a resposta dos ergorreflexos. Essa modulação reflexa pode ser responsável pelo aumento da tolerância ao esforço sem o aumento do consumo de oxigênio / In heart failure (HF), exercise intolerance is related to hemodynamic and neurohumoral alterations by the complex interaction of cardiovascular reflexes. The central and peripheral chemoreflex and the ergoreflex are involved in hyperventilation at rest and during exercise, contributing to exercise intolerance. The aims of the study were to assess the effect of beta-blocker (betab) therapy on the central and peripheral chemoreflexes and ergoreflex responses through ventilatory changes during the six-minute walk test (6MWT), and to assess the effect of betab optimized therapy on plasma catecholamines and B-type natriuretic peptide (BNP). We studied 15 male patients, 49.5 ± 2.5 years, diagnosed with HF for more than three months, never-treated with ßb, ejection fraction (LVEF) 25.9 ± 2.5%, functional class I-III (NYHA). These patients could be in use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists. All subjects underwent the following tests: cardiopulmonary exercise treadmill test according to the Naughton protocol, three randomized treadmill 6MWT with speed controlled by the patient (one with sensitization of central chemoreceptors, one with an awareness of peripheral chemoreceptors and another control in ambiental air - AA). Also all subjects underwent 6MWT with and without regional circulatory occlusion on the lower limb. Regarding laboratory tests, plasma catecholamines concentration at rest and BNP were also analyzed. Patients were then submitted to the institution standard drug therapy, with introduction and optimization of betab and were reassessed six months later. After optimization, there was a significant improvement in LVEF from 26 ± 2.5 to 33 ± 2.6 (p < 0.05); and a decrease in BNP levels (775 ± 163 to 257 ± 75, p < 0.01) and plasma catecholamines (598 ± 104 to 343 ± 40, p < 0.05). There was also a significant decrease in resting heart rate from 95.6 ± 4.5 to 69.0 ± 1.6 (p < 0.01) but O2 pulse at rest increased post optimization (3.7 ± 0.3 to 4.4 ± 0.3, p < 0.01). Regarding the peak exercise, there was a significant decrease in peak heart rate 144.0 ± 4.6 to 129.5 ± 4.2 (p < 0,05) and VE/VCO2 slope 29.4(25.8-36.2) to 24.6(22.5-27.5), p=0.03); and an increase in O2 pulse (11.9 ± 1.1 to 15.5 ± 0.8, p < 0.01), and exercise time (12.3 ± 1.3 to 16.1 ± 1.2, p=0.01), without, however, increasing oxygen consumption. There was significant difference in walked distance during the 6MWT between the two time points (before and after) in all analyzes, both control (AA) and for the sensitization of central and peripheral chemoreceptors. Also, there was a decreased ventilatory response in sensitization of chemoreflexes when compared with the control. The optimization of drug therapy in HF, especially with ßb, promotes hemodynamic, metabolic and neurohormonal improvements. This study, which examined the effect of therapy with betab on the response of the chemoreflexes and ergoreflex in HF patients, documented that ßb decreases the response of chemoreflexes during exercise in hypoxia and hypercapnia without, however, altering the ergoreflex response. This reflex modulation may be responsible for the increased exercise tolerance without increasing oxygen consumption

A intolerância ao exercício físico na insuficiência cardíaca (IC) está relacionada a alterações hemodinâmicas e neurohumorais pela complexa interação dos reflexos cardiovasculares. Os quimiorreflexos central e periférico e o ergorreflexo estão envolvidos na hiperventilação de repouso e durante o exercício, contribuindo para intolerância ao esforço. Os objetivos do estudo foram avaliar o efeito da terapêutica com beta-bloqueador (betab) na resposta dos quimiorreflexos central e periférico e do ergorreflexo por meio das alterações da resposta ventilatória durante o teste de caminhada de seis minutos (T6M); e avaliar o efeito da sua otimização também sobre as catecolaminas plasmáticas e peptídeo natriurético do tipo B (BNP). Foram estudados 15 pacientes masculinos, 49.5 ± 2.5 anos, com diagnóstico de IC há mais de 3 meses, sem histórico de tratamento com betab, com fração de ejeção (FEVE) 25.9 ± 2.5%, classe funcional I-III (NYHA). Estes pacientes poderiam estar em uso de inibidores da enzima conversora da angiotensina, bloqueadores do receptor da angiotensina II e antagonista do receptor da aldosterona. Todos os indivíduos realizaram testes: ergoespirométrico em esteira segundo o protocolo de Naughton, três T6M em esteira com controle de velocidade pelo paciente randomizados (um com sensibilização dos quimiorreceptores centrais, um com sensibilização dos quimiorreceptores periféricos e um controle em ar ambiente - AA). Também realizaram T6M com e sem oclusão circulatória regional em membro inferior. Em relação aos exames laboratoriais, foram feitas análises de catecolaminas plasmáticas em repouso e BNP. Os pacientes foram então submetidos a tratamento medicamentoso padrão da Instituição, com introdução e otimização da terapêutica com ßb e, após seis meses, foram reavaliados. Após otimização do betab, houve melhora significativa na FEVE, de 26 ± 2,5 para 33 ± 2,6 (p < 0,05); diminuição de níveis de BNP (775 ± 163 para 257 ± 75; p < 0,01) e de catecolaminas plasmáticas (598 ± 104 para 343 ± 40; p < 0,05). Foi também observada diminuição significativa na frequência cardíaca de repouso, de 95.6 ± 4.5 para 69.0 ± 1.6 (p < 0,01), e aumento do pulso de O2 de repouso (3.7 ± 0.3 para 4.4 ± 0.3; p < 0,01) pós betab. Em relação ao pico do esforço, houve diminuição significativa da frequência cardíaca, de pico 144.0 ± 4.6 para 129.5 ± 4.2 (p < 0,05), aumento do pulso de O2 (11.9 ± 1.1 para 15.5 ± 0.8; p < 0,01), diminuição do VE/VCO2 slope 29.4(25.8-36.2) para 24.6 (22.5-27.5); p=0,03) e aumento do tempo de exercício (12.3 ± 1.3 para 16.1 ± 1.2; p=0,01), sem, entretanto, aumento do consumo de oxigênio. Houve diferença significativa em relação à distância percorrida no T6M entre os dois momentos (pré e pós) em todas as análises, tanto controle (AA) quanto para a sensibilização dos quimiorreceptores centrais e periféricos, além de diminuição da resposta ventilatória nas sensibilizações dos quimiorreflexos quando comparados com o controle. A otimização da terapêutica medicamentosa na IC, especialmente com betab, promove melhora hemodinâmica, metabólica e neurohormonal. O presente estudo, que examinou os efeitos da terapêutica com betab na resposta dos quimiorreflexos e ergorreflexo em pacientes com IC, documentou que o betab diminui a resposta dos quimiorreflexos durante o exercício em hipóxia e hipercapnia sem, entretanto, alterar a resposta dos ergorreflexos. Essa modulação reflexa pode ser responsável pelo aumento da tolerância ao esforço sem o aumento do consumo de oxigênio / In heart failure (HF), exercise intolerance is related to hemodynamic and neurohumoral alterations by the complex interaction of cardiovascular reflexes. The central and peripheral chemoreflex and the ergoreflex are involved in hyperventilation at rest and during exercise, contributing to exercise intolerance. The aims of the study were to assess the effect of beta-blocker (betab) therapy on the central and peripheral chemoreflexes and ergoreflex responses through ventilatory changes during the six-minute walk test (6MWT), and to assess the effect of betab optimized therapy on plasma catecholamines and B-type natriuretic peptide (BNP). We studied 15 male patients, 49.5 ± 2.5 years, diagnosed with HF for more than three months, never-treated with ßb, ejection fraction (LVEF) 25.9 ± 2.5%, functional class I-III (NYHA). These patients could be in use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists. All subjects underwent the following tests: cardiopulmonary exercise treadmill test according to the Naughton protocol, three randomized treadmill 6MWT with speed controlled by the patient (one with sensitization of central chemoreceptors, one with an awareness of peripheral chemoreceptors and another control in ambiental air - AA). Also all subjects underwent 6MWT with and without regional circulatory occlusion on the lower limb. Regarding laboratory tests, plasma catecholamines concentration at rest and BNP were also analyzed. Patients were then submitted to the institution standard drug therapy, with introduction and optimization of betab and were reassessed six months later. After optimization, there was a significant improvement in LVEF from 26 ± 2.5 to 33 ± 2.6 (p < 0.05); and a decrease in BNP levels (775 ± 163 to 257 ± 75, p < 0.01) and plasma catecholamines (598 ± 104 to 343 ± 40, p < 0.05). There was also a significant decrease in resting heart rate from 95.6 ± 4.5 to 69.0 ± 1.6 (p < 0.01) but O2 pulse at rest increased post optimization (3.7 ± 0.3 to 4.4 ± 0.3, p < 0.01). Regarding the peak exercise, there was a significant decrease in peak heart rate 144.0 ± 4.6 to 129.5 ± 4.2 (p < 0,05) and VE/VCO2 slope 29.4(25.8-36.2) to 24.6(22.5-27.5), p=0.03); and an increase in O2 pulse (11.9 ± 1.1 to 15.5 ± 0.8, p < 0.01), and exercise time (12.3 ± 1.3 to 16.1 ± 1.2, p=0.01), without, however, increasing oxygen consumption. There was significant difference in walked distance during the 6MWT between the two time points (before and after) in all analyzes, both control (AA) and for the sensitization of central and peripheral chemoreceptors. Also, there was a decreased ventilatory response in sensitization of chemoreflexes when compared with the control. The optimization of drug therapy in HF, especially with ßb, promotes hemodynamic, metabolic and neurohormonal improvements. This study, which examined the effect of therapy with betab on the response of the chemoreflexes and ergoreflex in HF patients, documented that ßb decreases the response of chemoreflexes during exercise in hypoxia and hypercapnia without, however, altering the ergoreflex response. This reflex modulation may be responsible for the increased exercise tolerance without increasing oxygen consumption

<p>    </p> <p>Cerebrovascular diseases, such as stroke, constitute the most common life-threatening neurological disease in the United States. To support normal brain function, maintaining adequate brain perfusion (i.e., cerebral blood flow (CBF)) is important. Therefore, it is crucial to assess the brain perfusion so that early intervention in cerebrovascular diseases can be applied if abnormal perfusion is observed. The goal of my study is to develop metrics to measure the brain perfusion through modeling brain physiology using resting-state and task-based blood-oxygenation-level- dependent (BOLD) functional MRI (fMRI). My first and second chapters focused on deriving the blood arrival time using the resting-state BOLD signal. In the first chapters, we extracted the systemic low-frequency oscillations (sLFOs) in the fMRI signal from the internal carotid arteries (ICA) and the superior sagittal sinus (SSS). Consistent and robust results were obtained across 400 scans showing the ICA signals leading the SSS signals by about 5 seconds. This delay time could be considered as an effective perfusion biomarker that is associate with the cerebral circulation time (CCT). To further explore sLFOs in assessing dynamic blood flow changes during the scan, in my second chapter, a “carpet plot” (a 2-dimensional plot time vs. voxel) of scaled fMRI signal intensity was reconstructed and paired with a developed slope-detection algorithm. Tilted vertical edges across which a sudden signal intensity change took place were successfully detected by the algorithm and the averaged propagation time derived from the carpet plot matches the cerebral circulation time. Given that CO₂ is a vasodilator, controlling of inhaled CO₂ is able to modulate the BOLD signal, therefore, as a follow-up study, we focused on investigating the feasibility of using a CO₂ modulated sLFO signal as a “natural” bolus to track CBF with the tool developed from the second chapter. Meaningful transit times were derived from the CO₂-MRI carpet plots. Not only the timing, the BOLD signal deformation (the waveform change) under CO₂ challenge also reveals very useful perfusion information, representing how the brain react to stimulus. Therefore, my fourth chapter focused on characterizing the brain reaction to the CO₂ stimulus to better measure the brain health using BOLD fMRI. Overall, these studies deepen our understanding of fMRI signal and the derived perfusion parameters can potentially be used to assess some cerebrovascular diseases, such as stroke, ischemic brain damage, and steno-occlusive arterial disease in addition to functional activations. </p>

Introduction: Internal Carotid Stump Syndrome may be one of the possible causes of ischemic stroke (iCMP), as well as retinal infarction (RI). Syndrome of the occluded internal carotid (ACI) (stump syndrome) is a nosological unit, which is characterized by an onset of ipsilateral iCMP or RI of thromboembolic ethiology in patients with occlusion of ACI via the externa carotid or arteria ophthalmica. In my thesis, I have concentrated upon the specification of the stump syndrome, its diagnostics and treatment; furthermore I have assessed the appropriateness of surgical approach in comparison with conservative approach. Material and methods: A total of 621 patients with occlusion were treated in two centres in the course of five years. In a group of 40 patients, the ACI occlusion was detected sonographically, the length of the occluded ACI being >5 mm, with normal vasoreactivity based upon SPECT CO2 and excluded cardiogenic cause of iCMP. The patients were divided in two groups - surgical and conservative. Patients were monitored in 6-month intervals for the total period of four years. Results: No RI or iCMP were detected in the surgical group; one patient died six months after surgery. We observed one case of amaurosis fugax in the conservative group. Conclusion: Ultrasound examination is a fully sufficient...

The BOLD contrast employed in functional MRI studies is an ambiguous signal composed of changes in blood flow, blood volume and oxidative metabolism. In situations where the vasculature and metabolism may have been affected, such as in aging and in certain diseases, the dissociation of the more physiologically-specific components from the BOLD signal becomes crucial. The latest generation of calibrated functional MRI methods allows the estimation of both resting blood flow and absolute oxygen metabolism. The work presented here is based on one such proof-of-concept approach, dubbed QUO2, whereby taking into account, within a generalized model, both arbitrary changes in blood flow and blood O2 content during a combination of hypercapnia and hyperoxia breathing manipulations, yields voxel-wise estimates of resting oxygen extraction fraction and oxidative metabolism. In the first part of this thesis, the QUO2 acquisition protocol and data analysis were revisited in order to enhance the temporal stability of individual blood flow and BOLD responses, consequently improving reliability of the model-derived estimates. Thereafter, an assessment of the within and between-subject variability of the optimized QUO2 measurements was performed on a group of healthy volunteers. In parallel, an analysis was performed of the sensitivity of the model to different sources of random and systematic errors, respectively due to errors in measurements and choice of assumed parameters values. Moreover, the various impacts of the oxygen concentration administered during the hyperoxia manipulation were evaluated through a simulation and experimentally, indicating that a mild hyperoxia was beneficial. Finally, the influence of Alzheimer’s disease in vascular and metabolic changes was explored for the first time by applying the QUO2 approach in a cohort of probable Alzheimer’s disease patients and age-matched control group. Voxel-wise and region-wise differences in resting blood flow, oxygen extraction fraction, oxidative metabolism, transverse relaxation rate constant R2* and R2* changes during hypercapnia were identified. A series of limitations along with recommended solutions was given with regards to the delayed transit time, the susceptibility artifacts and the challenge of performing a hypercapnia manipulation in cohorts of elderly and Alzheimer’s patients. / Le contraste BOLD employé dans les études d’imagerie par résonance magnétique fonctionnelle (IRMf) provient d’une combinaison ambigüe de changements du flux sanguin cérébral, du volume sanguin ainsi que du métabolisme oxydatif. Dans un contexte où les fonctions vasculaires ou métaboliques du cerveau ont pu être affectées, tel qu’avec l’âge ou certaines maladies, il est crucial d’effectuer une décomposition du signal BOLD en composantes physiologiquement plus spécifiques. La dernière génération de méthodes d’IRMf calibrée permet d’estimer à la fois le flux sanguin cérébral et le métabolisme oxydatif au repos. Le présent travail est basé sur une telle technique, appelée QUantitative O2 (QUO2), qui, via un model généralisé, prend en considération les changements du flux sanguin ainsi que ceux en concentrations sanguine d’O2 durant des périodes d’hypercapnie et d’hyperoxie, afin d’estimer, à chaque voxel, la fraction d’extraction d’oxygène et le métabolisme oxydatif au repos. Dans la première partie de cette thèse, le protocole d’acquisition ainsi que la stratégie d’analyse de l’approche QUO2 ont été revus afin d’améliorer la stabilité temporelle des réponses BOLD et du flux sanguin, conséquemment, afin d’accroître la fiabilité des paramètres estimés. Par la suite, une évaluation de la variabilité intra- et inter-sujet des différentes mesures QUO2 a été effectuée auprès d’un groupe de participants sains. En parallèle, une analyse de la sensibilité du model à différentes sources d’erreurs aléatoires (issues des mesures acquises) et systématiques (dues aux assomptions du model) a été réalisée. De plus, les impacts du niveau d’oxygène administré durant les périodes d’hyperoxie ont été évalués via une simulation puis expérimentalement, indiquant qu’une hyperoxie moyenne était bénéfique. Finalement, l’influence de la maladie d’Alzheimer sur les changements vasculaires et métaboliques a été explorée pour la première fois en appliquant le protocole QUO2 à une cohorte de patients Alzheimer et à un groupe témoin du même âge. Des différences en terme de flux sanguin, fraction d’oxygène extraite, métabolisme oxydatif, et taux de relaxation transverse R2* au repos comme en réponse à l’hypercapnie, ont été identifiées au niveau du voxel, ainsi qu’au niveau de régions cérébrales vulnérables à la maladie d’Alzheimer. Une liste de limitations accompagnées de recommandations a été dressée en ce qui a trait au temps de transit différé, aux artéfacts de susceptibilité magnétique, de même qu’au défi que représente l’hypercapnie chez les personnes âgées ou atteintes de la maladie d’Alzheimer.

Introduction: Internal Carotid Stump Syndrome may be one of the possible causes of ischemic stroke (iCMP), as well as retinal infarction (RI). Syndrome of the occluded internal carotid (ACI) (stump syndrome) is a nosological unit, which is characterized by an onset of ipsilateral iCMP or RI of thromboembolic ethiology in patients with occlusion of ACI via the externa carotid or arteria ophthalmica. In my thesis, I have concentrated upon the specification of the stump syndrome, its diagnostics and treatment; furthermore I have assessed the appropriateness of surgical approach in comparison with conservative approach. Material and methods: A total of 621 patients with occlusion were treated in two centres in the course of five years. In a group of 40 patients, the ACI occlusion was detected sonographically, the length of the occluded ACI being >5 mm, with normal vasoreactivity based upon SPECT CO2 and excluded cardiogenic cause of iCMP. The patients were divided in two groups - surgical and conservative. Patients were monitored in 6-month intervals for the total period of four years. Results: No RI or iCMP were detected in the surgical group; one patient died six months after surgery. We observed one case of amaurosis fugax in the conservative group. Conclusion: Ultrasound examination is a fully sufficient...