The viability of using a slicer based integral field spectrograph (IFS) for high contrast observations has been under scrutiny due to the belief that the one dimensional coherence that persists along the slice to the point of sampling at the detector will cause the creation of secondary speckles that will not have the same characteristics as normal speckles, thus stopping us from calibrating them out. It has also been previously assumed that a suitably low differential wavefront error when moving slice to slice was not guaranteed by design. It was for these reasons that slicer based IFSs were not selected for the current generation of planet finding instruments. As part of the EPICS (Exo Planet Imaging Camera and Spectrograph for the E-ELT) design study it was decided that slicers should be re-investigated due to results from on sky observations suggesting these limitations did not exist. The purpose of this thesis was to determine whether there was validity to the concerns mentioned above and therefore to answer the question; Would implementing a slicer based integral field spectrograph limit the achievable contrast of an instrument designed for the direct detection of exoplanets? Chapter 1 gives a brief introduction into the field of exoplanet research. Charpter 2 describes the noise limiting direct detection of exoplanets and the ways to get around it. Chapter 3 gives an overview of the two types of IFS under investigation by the EPICS consortium. Chapter 4 looks into details of the EPICS instrument and the IFS design study that came about. Chapter 5 shows simulations performed for the aim of achieving better contrasts via post processing methods and accurate data reduction as well as simulations of slicer based integral field spectrographs. Experimental tests using a slicer and a preoptics setup designed to simulate the limiting noise are described in Chapter 6. Chapter 7 looks at using SINFONI for high contrast observations and Chapter 8 details the conclusions drawn from the work presented in this thesis, as well as possible extensions to it. The work performed in this thesis dispels the concerns about the continued one dimensional coherence up to the detecter and suggests that slicer based integral field spectrographs do not inherently limit the contrast achievable; Results from experiments fit well with the requirements for EPICS to achieve its goals. Simulations also supported the idea that secondary speckle noise should not be an issue for the slicer based IFS. This means that a slicer based IFS is a viable option for the EPICS instrument.

Background:Left ventricular function is particularly important to investigate since it has prognostic significance in some heart diseases such as aortic stenosis. One of the relatively new methods to evaluate this is deformation analysis that can produce a measure of global longitudinal strain with speckle-tracking.  Objective:The objective was to examine the possibility of measuring left ventricular longitudinal function in patients with aortic stenosis from ECG-gated computed tomography images with the new software Segment CT and investigate prevalence of its reduction. Additionally, a second objective was to evaluate the feasibility of global longitudinal strain analysis from ECG-gated computed tomography in comparison with echocardiography and ejection fraction in a subset of patients.  Material and methods:This study included 97 patients with severe aortic stenosis who underwent evaluation before planned treatment with transcatheter aortic valve implantation during 2016-2017 at Uppsala Hospital. Global strain was calculated from ECG-gated computed tomography and echocardiography with dedicated software. Results:Left ventricular function measured by global strain was impaired in all patients while ejection fraction was decreased in 31 %. Mean global longitudinal strain by ECG-gated computed tomography was -6.46±3.51 % and by echocardiography -10.69±4.23 %. The mean difference between the methods was 4.23 %, which was statistically significant (p=0.02) while the correlation was good (r=0.74). Conclusions:The strain analysis of ECG-gated computed tomography images was successful in less than a half of the patients. The results of the two methods showed good correlation but not agreement, further research is thus needed with a higher number of patients.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2017-06-12T13:51:00Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) RAIMY COSTA MARTINS.pdf: 1412873 bytes, checksum: 1a015a5d3ada01cbd7dea500b27c388a (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2017-06-12T13:51:13Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) RAIMY COSTA MARTINS.pdf: 1412873 bytes, checksum: 1a015a5d3ada01cbd7dea500b27c388a (MD5) / Made available in DSpace on 2017-06-12T13:51:13Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) RAIMY COSTA MARTINS.pdf: 1412873 bytes, checksum: 1a015a5d3ada01cbd7dea500b27c388a (MD5) Previous issue date: 2017-03-21 / O “coração atleta” é o termo designado para caracterizar as adaptações cardíacas funcionais e anatômicas secundárias ao treinamento físico intenso e prolongado em humanos e animais. O ecocardiograma desempenha papel fundamental em distinguir as adaptações fisiológicas secundárias ao exercício, outrossim, as recentes técnicas introduzidas como Speckle Tracking (Ste) têm permitido obter informações relevantes a respeito da função cardíaca em humanos atletas. Desta forma, objetivou-se avaliar por meio do ecocardiograma, a estrutura e função sistólica do ventrículo esquerdo de cães praticantes de pastoreio há no mínimo quatro meses, cinco a seis vezes por semana, de quatro a oito horas por dia. Para tanto, 31 cães foram divididos em dois grupos: grupo pastoreio (GP, n=15) e grupo sedentário (GS, n=16), avaliados em um único momento, em repouso, e posteriormente submetidas a análise de variância, multivariada (ANOVA), dois por dois, em nível de significância à 95% (p<0,05) e tendência à 90% (p<0.1). Os cães do GP apresentaram maiores valores de diâmetro interno do ventrículo esquerdo ao final da sístole (GP: 2,72 ± 0,09; GS: 2,43 ± 0,09; P<0,034) indicando predomínio isotônico desta atividade. O volume sistólico apresentou-se maior no GP (GP: 28,51 ± 2,20; GS: 22,13 ± 2,17; P<0,049), enquanto o índice de performance miocárdica do ventrículo esquerdo (GP: 0,37 ± 0,03; GS: 0,46 ± 0,03; P<0,028) e o movimento sistólico septal (GP: 0,13 ± 0,01; GS: 0,15 ± 0,01; P<0,044) foram menores em relação ao GS, indicando melhor função cardíaca sisto-diastólica nos cães de pastoreio. Por meio da técnica Ste foi possível observar diminuição dos valores de strain e ou strain rate de alguns segmentos nos cães do GP, nos sentidos radial, circunferencial, longitudinal e transversal em relação ao GS, indicando menor necessidade de deformação miocárdica para a manutenção da função sistólica. Os resultados encontrados indicam que as variáveis ecocardiográficas convencionais (estruturais e funcionais), teciduais e provenientes da técnica STe, foram complementares e fundamentais para a compreensão das adaptações cardiovasculares em cães de pastoreio. / The "athlete's heart" is the term designed to characterize functional and anatomic cardiac adaptations secondary to intense and prolonged physical training in humans and animals. The echocardiogram plays a fundamental role in distinguishing the physiological adaptations secondary to exercise, also, the recent techniques introduced as Speckle Tracking Echocardiography have allowed us to obtain relevant information regarding cardiac function in human athletes. The aim of this study was to evaluate the structure and systolic function of the left ventricle of dogs practicing herding for at least four months, five to six times a week, from four to eight hours a day using echocardiography. For this, 31 dogs were divided into two groups: herding group (GP, n=15) and sedentary group (GS, n=16), evaluated in a single moment, at rest, and then submitted the multivariate analysis of variance (ANOVA), two by two, at the level of significance at 95% (p<0,05) and tendency to 90% (p<0.1). The GP dogs showed higher values of internal diameter of the ventricle at the end of systole (GP: 2,72 ± 0,09; GS: 2,43 ± 0,09; P<0,034), indicating isotonic predominance of this activity. At respect functional adaptations variables, systolic volume was higher in GP (GP: 28,51 ± 2,20; GS: 22,13 ± 2,17; P<0,049), differently from myocardial performance index of the left ventricle (GP: 0,37 ± 0,03; GS: 0,46 ± 0,03; P<0,028) and septal systolic moviment to GS (GP: 0,13 ± 0,01; GS: 0,15 ± 0,01; P<0,044). By means of the Ste technique, it was possible to observe a decrease in the strain and or strain rate values in GP dogs, in the radial, circumferential, longitudinal and transverse directions in relation to GS, indicating a lower need for myocardial deformation to maintain systolic function. The results indicate that the conventional echocardiographic variables (structural and functional) and tissue, obtained by the STe technique, were complementary and essential for the understanding of cardiovascular adaptations in herding dogs.

La thèse est consacrée à la caractérisation mécanique des films minces à l'aide de mesures de déplacements par voie optique et traitements numériques. Les domaines d'études sont d'une part les contraintes résiduelles et d'autre part l'essai de traction. Les moyens de mesure employés sont la projection de franges et la photographie numérique de speckle.<br /><br />La projection de franges permet de mesurer la carte des déplacement hors-plan. Elle est adaptée à la mesure des contraintes résiduelles dans les films minces par analyses de courbure et/ou essais de gonflement. On montre suite à trois études expérimentales :<br />1. la précaution à prendre dans l'utilisation de la formule de Stoney même pour des bicouches libre-libre (SiO2/Si) ;<br />2. la présence de flambage dans les membranes bicouches comprimées encastré-encastré (SiO2/Si) ;<br />3. un parfait accord entre essais de gonflement et essais de nano-indentation pour des films tendus (polimiide).<br /><br />La photographie numérique de speckle permet de mesurer la carte des déplacements dans le plan. Elle est adaptée avec succès à un banc d'essais de traction conçu durant la thèse et spécialement dédié aux films minces. Un algorithme original de calcul a été développé pour obtenir une résolution subpixel. Les performances de l'algorithme sont comparées par des simulations et des expériences aux algorithmes classiques de corrélation. Sa rapidité et sa haute résolution permettent de calculer les cartes de déplacements en temps réel. Les déformations dans le plan en sont déduites et permettent le tracé des courbes contrainte/déformation puis le calcul du module d'Young E et du coefficient de Poisson v. Les matériaux choisis pour valider le banc d'essai sont le cuivre électrodéposé, matériaux ductile, puis le silicium monocristallin, matériaux fragile.

Background: The twisting motion of the left ventricle (LV), with clockwise rotation at the base and counter clockwise rotation at the apex during systole, is a vital part of LV function. Even though LV rotation has been studied for decades, the rotation pattern has not been described in detail. By the introduction of speckle tracking echocardiography measuring rotation has become easy of access. However, the axis around which the LV rotates has never before been assessed. The aims of this thesis were to describe the rotation pattern of the LV in detail (study I), to assess RV apical rotation (study II), develop a method to assess the rotation axis (study III) and finally to study the effect of regional ischemia to the rotation pattern of the LV (study IV). Methods: Healthy humans were examined in study I-III and the final study populations were 40 (60±14 years), 14 (62±11 years) and 39 (57±16 years) subjects, respectively. In study IV six young pigs (32-40kg) were studied. Standard echocardiographic examinations were performed. In study IV the images were recorded before and 4 minutes after occlusion of left anterior descending coronary artery (LAD). Rotation was measured in short axis images by using a speckle tracking software. By development of custom software, the rotation axis of the LV was calculated at different levels in every image frame throughout the cardiac cycle. Results: Study I showed significant difference in rotation between basal and apical rotations, as well as significant differences between segments at basal and mid ventricular levels. The rotation pattern of the LV was associated with different phases of the cardiac cycle. Study II found significant difference in rotation between the LV and the RV. RV rotation was heterogeneous and bi-directional, creating a ´tightening belt action´ to reduce it circumference. Study III indicated that the new method could assess the rotation axis of the LV. The motion of the rotation axes in healthy humans displayed a physiological and consistent pattern. Study IV found a significant difference in the rotation pattern, between baseline and after LAD occlusion, by measuring the rotation axes, but not by conventional measurements of rotation. AV-plane displacement and wall motion score (WMS) were also significantly changed after inducing regional ischemia. Conclusion: There are normally large regional differences in LV rotation, which can be associated anatomy, activation pattern and cardiac phases, indicating its importance to LV function. In difference to the LV, the RV did not show any functional rotation. However, its heterogeneous circumferential motion could still be of importance to RV function and may in part be the result of ventricular interaction. The rotation axis of the LV can now be assessed by development of a new method, which gives a unique view of the rotation pattern. The quality measurements and results in healthy humans indicate that it has a potential clinical implication in identifying pathological rotation. This was supported by the experimental study showing that the rotation axis was more sensitive than traditional measurements of rotation and as sensitive as AV-plane displacement and WMS in detecting regional myocardial dysfunction.

We aim to develop an implantable, optical neural imaging device by fabricating lasers and photodiodes onto a gallium arsenide substrate. Some studies suggest that lasers exhibit higher noise than light emitting diodes (LEDs) due to coherence effects – my studies aim to quantify this noise and to guide device development. To this end, I developed a model of a fluorescent imaging device which agreed with experiment. Noise analysis performed in phantom showed that laser sources exhibit temporal and spatial noise up to 10x higher than LED sources, and in vivo noise analysis also demonstrated this trend. I studied a neural injury model called cortical spreading depression in vitro in mouse brain slices and in vivo in the rat brain using laser and LED sources. Signal magnitudes in vitro are on the order of 10% and in vivo results are inconclusive. Future work will aim to reduce coherence related noise.

Background:  The right ventricle (RV) is multi-compartmental in orientation with a complex structural geometry. However, assessment of this part of the heart has remained an elusive clinical challenge. As a matter of fact, its importance has been underestimated in the past, especially its role as a determinant of cardiac symptoms, exercise capacity in chronic heart failure and survival in patients with valvular disease of the left heart. Evidence also exists that pulmonary hypertension (PH) affects primarily the right ventricular function. On the other hand, previous literature suggested that severe aortic stenosis (AS) affects left ventricular (LV) structure and function which partially recover after aortic valve replacement (AVR). However, the impact of that on RV global and segmental function remains undetermined.  Objectives: We sought to gain more insight into the RV physiology using 3D technology, Speckle tracking as well as already applicable echocardiographic measures. Our first aim was to assess the normal differential function of the RV inflow tract (IT), apical and outflow tract (OT) compartments, also their interrelations and the response to pulmonary hypertension. We also investigated the extent of RV dysfunction in severe AS and its response to AVR. Lastly, we studied the extent of global and regional right ventricular dysfunction in patients with pulmonary hypertension of different aetiologies and normal LV function. Methods: The studies were performed on three different groups; (1) left sided heart failure with (Group 1) and without (Group 2) secondary pulmonary hypertension, (2) severe aortic stenosis and six months post AVR and (3) pulmonary hypertension of different aetiologies and normal left ventricular function. We used 3D, speckle tracking echocardiography and conventionally available Doppler echocardiographic transthoracic techniques including M-mode, 2D and myocardial tissue Doppler. All patients’ measurements were compared with healthy subjects (controls). Statistics were performed using a commercially available SPSS software. Results: 1-  Our RV 3D tripartite model was validated with 2D measures and eventually showed strong correlations between RV inflow diameter (2D) and end diastolic volume (3D) (r=0.69, p&lt;0.001) and between tricuspid annular systolic excursion (TAPSE) and RV ejection fraction (3D) (r=0.71, p&lt;0.001). In patients (group 1 &amp; 2) we found that the apical ejection fraction (EF) was less than the inflow and outflow (controls:  p&lt;0.01 &amp; p&lt;0.01, Group 1:  p&lt;0.05 &amp; p&lt;0.01 and Group 2: p&lt;0.05 &amp; p&lt;0.01, respectively). Ejection fraction (EF) was reduced in both patient groups (p&lt;0.05 for all compartments). Whilst in controls, the inflow compartment reached the minimum volume 20 ms before the outflow and apex, in Group 2 it was virtually simultaneous. Both patient groups showed prolonged isovolumic contraction (IVC) and relaxation (IVR) times (p&lt;0.05 for all). Also, in controls, the outflow tract was the only compartment where the rate of volume fall correlated with the time to peak RV ejection (r = 0.62, p = 0.03). In Group 1, this relationship was lost and became with the inflow compartment (r = 0.61, p = 0.01). In Group 2, the highest correlation was with the apex (r=0.60, p&lt;0.05), but not with the outflow tract. 2- In patients with severe aortic stenosis, time to peak RV ejection correlated with the basal cavity segment (r = 0.72, p&lt;0.001) but not with the RVOT. The same pattern of disturbance remained after 6 months of AVR (r = 0.71, p&lt;0.001). In contrast to the pre-operative and post-operative patients, time to RV peak ejection correlated with the time to peak outflow tract strain rate (r = 0.7, p&lt;0.001), but not with basal cavity function. Finally in patients, RVOT strain rate (SR) did not change after AVR but basal cavity SR fell  (p=0.04). 3- In patients with pulmonary hypertension of different aetiologies and normal LV function, RV inflow and outflow tracts were dilated (p&lt;0.001 for both). Furthermore, TAPSE (p&lt;0.001), inflow velocities (p&lt;0.001), basal and mid-cavity strain rate (SR) and longitudinal displacement (p&lt;0.001 for all) were all reduced. The time to peak systolic SR at basal, mid-cavity (p&lt;0.001 for both) and RVOT (p=0.007) was short as was that to peak displacement (p&lt;0.001 for all). The time to peak pulmonary ejection correlated with time to peak SR at RVOT (r=0.7, p&lt;0.001) in controls, but with that of the mid cavity in patients (r=0.71, p&lt;0.001). Finally, pulmonary ejection acceleration (PAc) was faster (p=0.001) and RV filling time shorter in patients (p=0.03) with respect to controls. Conclusion: RV has distinct features for the inflow, apical and outflow tract compartments, with different extent of contribution to the overall systolic function. In PH, RV becomes one dyssynchronous compartment which itself may have perpetual effect on overall cardiac dysfunction. In addition, critical aortic stenosis results in RV configuration changes with the inflow tract, rather than outflow tract, determining peak ejection. This pattern of disturbance remains six month after valve replacement, which confirms that once RV physiology is disturbed it does not fully recover. The findings of this study suggest an organised RV remodelling which might explain the known limited exercise capacity in such patients. Furthermore, in patients with PH of different aetiologies and normal LV function, there is a similar pattern of RV disturbance. Therefore, we can conclude that early identification of such changes might help in identifying patients who need more aggressive therapy early on in the disease process.

We aim to develop an implantable, optical neural imaging device by fabricating lasers and photodiodes onto a gallium arsenide substrate. Some studies suggest that lasers exhibit higher noise than light emitting diodes (LEDs) due to coherence effects – my studies aim to quantify this noise and to guide device development. To this end, I developed a model of a fluorescent imaging device which agreed with experiment. Noise analysis performed in phantom showed that laser sources exhibit temporal and spatial noise up to 10x higher than LED sources, and in vivo noise analysis also demonstrated this trend. I studied a neural injury model called cortical spreading depression in vitro in mouse brain slices and in vivo in the rat brain using laser and LED sources. Signal magnitudes in vitro are on the order of 10% and in vivo results are inconclusive. Future work will aim to reduce coherence related noise.

The roles of the vascular architecture and blood flow in response to neurovascular diseases are important in predicting physiological outcomes. Observing these parameters chronically with optical imaging techniques provides insight into the neurovascular recovery process. We develop and deploy optical imaging systems for monitoring the progression of vascular structure, perfusion, and functional blood response after ischemic stroke in a chronic rodent model to observe vascular dynamics of the cortex under normal and diseased pathologies. Specifically, we monitor the progression of the vascular structure and cerebral blood flow (CBF) over a chronic period in the rodent cortex after photo-thrombotic occlusion. Multi-Exposure Speckle Imaging (MESI) provides surface measurements of microvascular flow dynamics while Two-Photon Fluorescence Microscopy offers direct visualization of the microvascular structure. We observe the occurrence of vascular reorientation in the sub-surface microvascular structure over a 35 day post-occlusion period. We also correlate MESI flow estimates in the parenchyma with sub-surface microvascular volume fractions from two-photon microscopy to assess how vascular density influences the surface-integrated MESI measurements. Next, we develop and validate a MESI technique for measuring absolute changes of the functional blood flow response to forepaw stimulation in rodents, termed FA MESI. The optimal camera exposures for capturing the CBF response to forepaw stimulation are extracted from a training set of animal data and the feasibility of the technique is demonstrated in a testing animal set by comparing functional response results between new and existing techniques. We then deploy this system in a chronic study monitoring the progression of hemodynamic parameters after ischemic stroke within the functionally responding area of the cortex. The progression of the regional CBF perfusion and absolute changes in the magnitude of the functional blood flow response are monitored chronically after photo-thrombotic occlusion. We compare the differences between absolute and relative measurements of the functional blood flow responses, and validate FA MESI by comparing baseline measurements to 15-exposure MESI over the sampled flow distributions. We demonstrate the differences measured between the functional outcomes and the regional CBF perfusion over a three week post-occlusion time period. / text

This dissertation presents the development and use of a novel optical imaging system capable of monitoring changes in blood flow, oxygenated hemoglobin, deoxygenated hemoglobin, and absolute pO₂ in the brain. There are several imaging modalities capable of monitoring these parameters separately. Laser speckle contrast imaging (LSCI) and multi-spectral reflectance imaging (MSRI) have been used to monitor relative blood flow and hemoglobin changes respectively. Phosphorescence quenching, while not typically used for imaging, is capable of noninvasive measurements of pO₂. Combining these three techniques has led to the development of an imaging system that could ultimately lead to a better understanding of brain physiology. By combining techniques such as LSCI and MSRI, it becomes possible to estimate the cerebral metabolic rate of oxygen (CMRO₂), an important indicator of neuronal function. It is equally important to understand absolute pO₂ levels so that oxygen metabolism can be examined in context. Integrating phosphorescence quenching and a spatial light modulator into the imaging system allowed absolute pO₂ to be simultaneously measured in distinct regions. This new combined system was used to investigate pathophysiological conditions such as cortical spreading depression (CSD) and ischemia. The observed hemodynamic changes associated with these events were largely dictated by baseline oxygen levels and varied significantly in different regions. This finding highlighted the importance of having a system capable of monitoring hemodynamic changes and absolute pO₂ simultaneously while maintaining enough spatial resolution to distinguish the changes in different regions. It was found that animals with low baseline pO₂ were unable to deliver enough oxygen to the brain during events like CSD because of the high metabolic demand. In order for this technique to become more prevalent among researchers, it is essential to make it cost effective and simple to use. This was accomplished by replacing the expensive excitation sources with cheaper light emitting diodes (LEDs) and redesigning the software interface so that it was easier to control the entire device. The final system shows the potential to become a key tool for researchers studying the role of absolute pO₂ and other hemodynamic parameters during pathophysiological conditions such as CSD and ischemia. / text