Heidelberg, Univ., Diss., 2007.

Techn. Hochsch., Diss., 2003--Aachen.

Techn. Universiẗat, Diss., 2006--Darmstadt.

It is well known now that there exists a coupling between functional brain activity and regional blood flow response in the somatosensory cortex and other cortical areas. Various modalities, including functional magnetic resonance imaging and optical imaging (intrinsic signals as well as fluorescence), have been developed in the past to map functional brain activity. The complexity and fundamental physical constraints of the instruments preclude functional imaging in awake, behaving small animals. This thesis presents the method of Laser Speckle Imaging (LSI) of brain with high spatial and temporal resolution, and potential for imaging awake and behaving animals. The method has the potential to map brain activation with high sensitivity and spatiotemporal resolution without using any exogenous contrast agents. In LSI, scattered laser light with different paths produces a random interference pattern known as speckle, fluctuations of which contain information about the motion of particles in the underlying medium. A post-processing step is needed to extract information out of the speckle images, two of which we introduce in details. Our first method is based on Laser speckle contrast analysis (LASCA), which has been demonstrated as a full-field method for imaging the cerebral blood flow (CBF). However, conventional LASCA is limited to extremely low dynamic range because of the ambient background field, dark current and anomalies in the circuits of CCD camera, which makes it difficult to analyze the spatiotemporal variabilities in CBF. In this study, we propose an enhanced laser speckle contrast analysis (eLASCA) method to improve the dynamic range of LASCA based on monotonic point transformation (MPT). In addition, eLASCA greatly improves the CBF visualization, which is very helpful in demonstrating the details of CBF change. Our second method involves the second order features (SOFs) of the image; they are derived from the cooccurrence matrix that in turn was calculated over the same spatial and temporal window than for the contrast. The image quality metrics - equivalent number of looks, entropy and objective quality – showed superior performance of the SOFs comparing to the contrast analysis. / --

Background: Hereditary transthyretin amyloidosis (ATTR) is a lethal disease in which misfolded transthyretin (TTR) proteins accumulate as insoluble aggregates in tissues throughout the body. A common mutation is the exchange of valine to methionine at place 30 (TTR V30M), a form endemically found in the northern parts of Sweden. The main treatment option for ATTR amyloidosis is liver transplantation as the procedure halts production of mutated transthyretin. The disease is associated with marked phenotypic diversity ranging from predominant cardiac complications to pure neuropathy. Two different types of fibril composition – one in which both fragmented and full-length TTR are present (type A) and one consisting of only full-length TTR (type B) have been suggested to account for some phenotypic differences. Cardiac amyloidosis is associated with increased myocardial thickness and the disease could easily be mistaken for other entities characterised by myocardial thickening, such as sarcomeric hypertrophic cardiomyopathy (HCM). The aims in this thesis were to investigate echocardiographic characteristics in Swedish ATTR amyloidosis patients, and to identify markers aiding in differentiating ATTR heart disease from HCM. Another objective was to examine the impact of fibril composition and sex on the phenotypic variation in amyloid heart disease. Methods: A total of 122 ATTR amyloidosis patients that had undergone thorough echocardiographic examinations were included in the studies. Analyses of ventricular geometry as well as assessment of systolic and diastolic function were performed, using both conventional echocardiographic methods and speckle tracking technique. ECG analysis was conducted in study I, allowing measurement of QRS voltage. In study I and study II ATTR patients were compared to patients with HCM. In addition, 30 healthy controls were added to study II. Results: When parameters from ECG and echocardiography were investigated, the results revealed that the combination of QRS voltage <30 mm (<3 mV) and an interventricular/posterior wall thickness quotient <1.6 could differentiate cardiac ATTR amyloidosis from HCM. Differences in degree of right ventricular involvement were also demonstrated between HCM and ATTR amyloidosis, where ATTR patients displayed a right ventricular apical sparing pattern whereas the inverse pattern was found in HCM. Analysis of fibril composition revealed increased LV wall thickness in type A patients compared to type B, but in addition type A women displayed both lower myocardial thickness and more preserved systolic function as compared to type A males. When cardiac geometry and function were evaluated pre and post liver transplantation in type A and B patients, significant deterioration was detected in type A but not in type B patients after liver transplantation. Conclusions: Increasing awareness of typical cardiac amyloidotic signs by echocardiography is important to reduce the risk of delayed diagnosis. Our classification model based on ECG and echocardiography could aid in differentiating ATTR amyloidosis from HCM. Furthermore, the apical sparing pattern found in the right ventricle may pose another clue for amyloid heart disease, although it requires to be studied further. Furthermore, we disclosed that type A fibrils, male sex and increasing age were important determinants of increased myocardial thickness. As type A fibril patients displayed rapid cardiac deterioration after liver transplantation other treatment options should probably be sought for this group of patients.

Speckle tracking echocardiography (STE) is a relatively new imaging modality that enables the direct measurement of active contractile myocardial tissue in an offline analysis. This is accomplished through a software algorithm that tracks collections of acoustic markers, known as 'speckles', that are unique to a given section of myocardium. By measuring the displacement of these 'speckles' as the heart contracts and relaxes, STE produces parameters of the strain, or percent change in length, exhibited by the myocardium. As multiple studies have shown, this strain data produced by tracking of the global left atrium has the ability to accurately assess the physiologic functions of the atrium as a reservoir, conduit and booster pump in the cardiac cycle. Despite these valuable correlations, there are noted problems with STE regarding acoustic cluttering and disappearance of 'speckles' that can occur as the selected region of interest moves out of the field of view or becomes obscured. These problems may be increased when tracking an extended region of myocardium. Therefore, this present study sought to test a new method of assessing left atrial function with STE strain analysis by focusing on a concise region of the atrium, specifically the interatrial septum. To test this, the echocardiograms of 37 patients were obtained and grouped according to the designation of their cardiac function as normal (n=11), abnormal (n=12), or exhibiting signs of cardiac amyloidosis (n=14). In all patients, STE strain analysis was performed on the both the global left atrium and the interatrial septum. Measurements of the mean peak strain observed in the resultant strain curves were recorded for both STE scans of each patient. The curves produced by the tracking the segments of the entire atrium (6 segments) and interatrial septum (3 segments) were compared based on the exhibited changes in strain seen in the relative shapes of the curves, as well as the spread of the segmental strain curves about the calculated mean strain curve. Additionally, the number of segments that were either unsuccessfully or incorrectly tracked was recorded as a measure of the accuracy of STE. As a final step, the interatrial strain curves of four selected patients in the various states of ventricular diastolic dysfunction were chosen and compared with data obtained from scans of mitral flow echocardiography and tissue Doppler imaging (TDI) in an attempt to correlate the exhibited changes in strain shown in the interatrial septum with the physiologic functions of the atrium during ventricular diastole. The results showed that the mean peak strain of the global atrial strain trace decreased from normal (41.32%±10.8) to abnormal (21.69%±13.8) to the amyloid group (10.41%±6.9). This trend was echoed in the mean peak strain measured in the interatrial septum, as measured in normal (64.2%±15.6), abnormal (28.37%±13.4) and amyloid groups (12.21%±12.1). When the strain curves of the entire atrium and interatrial septum were compared, they demonstrated similar patterns in the timing of changes in strain, however the strain curves of the individual interatrial septum segments showed a much more concise grouping about the mean strain curve and were less likely to exhibit discordant segmental strain curves that deviated from the pattern established by all other segments in the trace. Additionally, within the STE scans of the global atrium, the interatrial septum exhibited a higher percentage of successfully tracked segments than did the lateral atrial wall; this trend was universally exhibited in all three groups. Finally, the interatrial septum strain curves, mitral flow echocardiography and TDI scans all demonstrated similar indications of left atrial function in the four selected patients. Ultimately, STE strain analysis of the interatrial septum appears to be a more accurate method of tracking the atrial myocardium than STE tracing of the global left atrium. Furthermore, it shows viable potential as a method for assessing the global physiologic function of the left atrium, as indicated by the similarities between the trends exhibited by these STE scans and the data gathered from scans produced by mitral flow echocardiography and TDI.

xxv, 207 p. ; ill. (some col.) A print copy of this title is available from the UO Libraries, under the call number: SCIENCE QD172.T6 T87 2008 / A growing interest in the physics of complex systems such as in the transition-metal oxide family has exploded recently, especially in the last 20 years or so. One notable effect is the change in electrical resistivity of a system by orders of magnitude in an applied magnetic field, coined the "colossal magnetoresistance effect". In efforts to understand these types of effects, there has been an unveiling of a rich variety of phenomena in the field of strongly correlated electron physics that has come to dominate the current scientific times. Most notable is the competition of myriad types of order: magnetic, lattice, charge and orbital all self-organize to display a fascinating array of phases on a variety of length scales. Furthermore, it has become apparent that new probes are needed to grasp some of this physics that transcends current condensed matter theory, where much of the behavior of these types of systems has remained unexplored. We have developed a new technique to gain more information about the system than with conventional x-ray diffraction. By scattering highly coherent, low energy x-rays, we can measure manganite speckle: a "fingerprint' of the microscopic structure in the bulk. The coherence of the x-rays can further be used to elucidate new insight into the dynamics of these phases. We describe here a number of novel effects near the orbital order phase transition in a half-doped manganite. We observe a small fluctuating component in the scattered signal that is correlated with three effects: both a rapidly decreasing total signal and orbital domain size, as well as an abrupt onset of a broad background intensity that we attribute to the thermal production of correlated polarons. Our results suggest that the transition is characterized by a competition between a pinned orbital domain topology that remains static, and mobile domain boundaries that exhibit slow, spatiotemporal fluctuations. This study opens up a new chapter to the study of manganite physics as coherent x-ray scattering offers a new direction to understand the strange and exotic behavior demonstrated in the multifaceted manganites. / Adviser: Stephen Kevan

Nous proposons dans cette thèse d’étudier une méthode d’imagerie qui s’adapte à la scène étudiée en utilisant des états polarimétriques choisis sur critères physiques pour optimiser le contraste polarimétrique en 2 zones aux propriétés polarimétriques différentes. En prenant en compte le bruit de Grenaille du détecteur, cette nouvelle technique d’imagerie à 2 canaux nommée APSCI montre un gain en contraste quantifié par la distance de Bhattacharyya pouvant atteindre un facteur 10 par rapport à l’imagerie de Mueller. D’autre part, elle utilise la totalité de l’information polarimétrique de la scène pour générer une seule image au contraste optimum ce qui la rend particulièrement performante pour distinguer deux zones aux propriétés polarimétriques légèrement différentes. La solution analytique complète de ce problème est proposée au chapitre suivant avec des illustrations associées. Le modèle proposé permet, en plus d’une interprétation physique, de quantifier les performances limites de la méthode APSCI en fonction des matrices de Mueller des 2 objets à discerner. Le chapitre suivant est consacré à l’étude des performances de cette méthode soumise au bruit optique de tavelure de cible. Les simulations numériques montrent que les performances de cette méthode en terme de contraste polarimétrique restent relativement robustes et souvent très supérieures à celles obtenues par l’imagerie de Mueller classique. Le dernier chapitre consiste à décrire l’implémentation expérimentale nécessaire à l’adaptation d’un imageur de Mueller en imageur APSCI en vue d’obtenir un imageur hybride Mueller/APSCI. La méthode APSCI nécessite de pouvoir utiliser en émission et en projection lors de la détection. / We propose in this thesis to study and imaging method which is adapted to the scene under investigation by the use of specific polarimetric excitations. The scenes under inversigation have two separate regions with different polarimetric properties. The specific fully polarized state of illumination is found by the physical criteria for oprimizing the polarimetric constrat in two aereas with different polarization properties. Taking into account the Shot noise of the detector, this new 2 channel imaging technique named APSCI, shows a gain in contrast quantified by the Bhattacharyya distance of up to a factor of 10 compared to what is achievable from classical Mueller imagnin. On the other hand, it uses the full polarimetric information of the scene to generate a single image at optimum contrast which makes it particularly effective to distinguish two distinct areas with slightly different polarization properties. The complete analytical solution of this problem is proposed in the next chapter with associated illustrations. The proposed model allows, in addition to a physical interpretation of the imaging problem, to quantify the limits of APSCI method based on evaluated Mueller matrices of the scene. Furthermore the relative performance of APSCI vs Classical Mueller Imaging (CMI) associated to polar decomposition has been studied numerically. Finally we have setup an hybrid CMI-APSCI imaging setup by indigenous calibration technique with a polarimetric precession of approximately 1% when room temperature varies around 1 degree C.

Doctor of Philosophy / Department of Mechanical and Nuclear Engineering / B. Terry Beck / The current experimental method to determine the transfer length in prestressed concrete members consists of measuring concrete surface strains before and after de-tensioning with a mechanical strain gage. The method is prone to significant human errors and inaccuracies. In addition, since it is a time-consuming and tedious process, transfer lengths are seldom if ever measured on a production basis. A rapid, non-contact method for determining transfer lengths in prestressed concrete members has been developed. The new method utilizes laser-speckle patterns that are generated and digitally recorded at various points along the prestressed concrete member. User-friendly software incorporating robust and fast digital image processing algorithms was developed by the author to extract the surface strain information from the captured speckle patterns. Based on the laser speckle measurement technique, four (4) successively improved generations of designs have been made. A prototype was fabricated for each design either on an optical breadboard for concept validation, or in a portable self-contained unit for field testing. For each design, improvements were made based on the knowledge learned through the testing of the previous version prototype. The most recent generation prototype, incorporating a unique modular design concept and self-calibration function, has several preferable features. These include flexible adjustment of the gauge length, easy expansion to two-axis strain measurement, robustness and higher accuracy. Extensive testing has been conducted in the laboratory environment for validation of the sensor’s capability in concrete surface strain measurement. The experimental results from the laboratory testing have shown that the measurement precision of this new laser speckle strain measurement technique can easily achieve 20 microstrain. Comparison of the new sensor measurement results with those obtained using traditional strain gauges (Whittemore gauge and the electrical resistance strain gauge) showed excellent agreement. Furthermore, the laser speckle strain sensor was applied to transfer length measurement of typical prestressed concrete beams for both short term and long term monitoring. The measurement of transfer length by the sensor was unprecedented since it appears that it was the first time that laser speckle technique was applied to prestressed concrete inspection, and particularly for use in transfer length measurement. In the subsequent field application of the laser speckle strain sensor in a CXT railroad cross-tie plant, the technique reached 50 microstrain resolution, comparable to what could be obtained using mechanical gauge technology. It was also demonstrated that the technique was able to withstand extremely harsh manufacturing environments, making possible transfer length measurement on a production basis for the first time.

Ferramentas diagnósticas capazes de detectar envolvimento cardíaco precoce na doença de Chagas são necessárias. A técnica ecocardiográfica de rastreamento de pontos, ou speckle tracking echocardiography (STE) oferece condições para o diagnóstico precoce de lesão cardíaca por avaliar a deformação miocárdica (strain). O objetivo do estudo foi avaliar as alterações sequenciais de parâmetros estruturais e funcionais dos ventrículos na evolução da doença. Um total de 37 hamsters fêmeas (Mesocricetus auratus) adultas receberam, por via intraperitoneal, 35.000 formas tripomastigotas de Trypanosoma cruzi (grupo Chagas) e outras 20 receberam igual volume de solução salina (grupo controle). Ecocardiograma foi realizado imediatamente antes da infecção (exame basal) e repetido para avaliação das fases aguda (1 mês) e crônica (4, 6 e 8 meses após). Foram avaliados: diâmetros do ventrículo esquerdo (DDFVE e DSFVE), fração de ejeção (FEVE), strain longitudinal (GLS), circunferencial (GCS) e radial (GRS) do ventrículo esquerdo e TAPSE, índice de função sistólica do ventrículo direito. A avaliação das diferenças entre os dois grupos ao longo de tempo foi realizada por meio da análise de variância (ANOVA) para modelos mistos de medidas repetidas. Ao exame basal, os dois grupos apresentaram idade média de 89 ± 1 dias. Os animais do grupo controle apresentaram peso de 130 ± 15 gramas; frequência cardíaca de 204 ± 18 batimentos/minuto, enquanto os do grupo Chagas apresentaram peso de 143 ± 12 gramas e frequência cardíaca de 198 ± 18 batimentos/minuto. Os valores de peso foram significativamente diferentes (p= 0,004) entre os grupos, mas não os de frequência cardíaca. A fração de ejeção do ventrículo esquerdo foi de 64 ± 5 % no grupo controle e de 61 ± 5 % no grupo Chagas, p= 0,10, enquanto o GLS foi de -15,2 ± 2,7 % no grupo controle e de -14,2 ± 3,4 % no grupo Chagas, p= 0,25. Na evolução da doença, o grupo Chagas apresentou aumento do DSFVE significativamente maior do que o aumento mostrado pelo grupo controle (valor-p da interação grupos#tempo= 0,007); a FEVE mostrou queda progressiva ao longo do tempo no grupo Chagas, com diferença verificada entre os grupos a partir de 6 meses do exame basal (valor-p da interação grupos#tempo= 0,005). O GLS e o GCS dos animais do grupo Chagas apresentaram comportamento significativamente diferente ao longo do tempo em comparação com o grupo controle (valor-p da interação grupos#tempo= 0,003 para o GLS e < 0,001 para oGCS). Para ambos, a diferença entre os grupos é verificada a partir do primeiro mês, quando se detecta queda pronunciada desses parâmetros de deformação. O índice TAPSE do grupo Chagas apresentou comportamento significativamente diferente ao longo do tempo em comparação ao grupo controle (valor-p da interação grupos#tempo < 0,009), com diferença observada a partir do primeiro mês. Diante disso, os resultados revelam que o GLS e o GCS são os parâmetros mais sensíveis para a avaliação funcional do ventrículo esquerdo na fase aguda e na fase crônica da doença de Chagas no modelo estudado. / Diagnostic tools capable to detect early heart involvement in Chagas\' disease are necessary. The speckle tracking echocardiography (STE) provides conditions for early diagnosis of cardiac lesion by evaluating myocardial deformation (strain). The objective of this study was to evaluate the sequential changes of structural and functional parameters of the ventricles in the evolution of the disease. A total of 37 adult female hamsters (Mesocricetus auratus) were inoculated intraperitoneally with 35,000 trypomastigote forms of Trypanosoma cruzi (Chagas group) and another 20 received equal volume of saline solution (control group). Echocardiography was performed before the infection (baseline) and repeated for assessment of acute (1 month) and chronic (4, 6 and 8 months after) phases. Left ventricular end-diastolic (LVED), left ventricular end-systolic (LVES), left ventricular ejection fraction (LVEF) and longitudinal strain (GLS) were measured at parasternal long-axis view. Circumferential strain (GCS) and radial strain (GRS) were evaluated at short-axis view (mid-LV cavity). Tricuspid annular plane systolic excursion (TAPSE) was used to assess right ventricular function. The analysis of variance (ANOVA) for mixed models of repeated measures was used to evaluate the differences between the two groups over time. At baseline, the two groups had a mean age of 89 ± 1 days. The animals in the control group had a weight of 130 ± 15 grams; heart rate of 204 ± 18 beats/minute, while those in the Chagas group had a weight of 143 ± 12 grams and a heart rate of 198 ± 18 beats/minute. The weight values were significantly different (p = 0.004) between the groups, but not those of heart rate. Left ventricular ejection fraction was 64 ± 5% in the control group and 61 ± 5% in the Chagas group (p = 0.10), while GLS was -15.2 ± 2.7% in the control group and of -14.2 ± 3.4% in the Chagas group (p = 0.25). In the evolution of the disease, the Chagas group presented a significantly higher increase in the LVES than the increase shown by the control group (p-value of the interaction groups # time = 0.007); the LVEF showed progressive decrease over time in the Chagas group, with a difference between groups after 6 months of baseline examination (p-value of interaction groups # time = 0.005). The GLS and GCS of the animals of the Chagas group showed significantly different behavior over time compared to the control group (p-value of the interaction groups # time = 0.003 for GLS and <0.001 for GCS). For both, the difference between groups is verified from the first month, when a pronounced decrease of these deformation parameters is detected. The TAPSE index of the Chagas group presented a significantly different behavior over time compared to the control group (p-value of interaction groups # time <0.009), with difference observed from the first month. Therefore, the results indicate that GLS and GCS are the most sensitive parameters for left ventricle functional assessment in acute and chronic phases of an experimental model of Chagas disease.