[Truncated abstract] Purpose: To improve our ability to interpret and validate Heidelberg Retina Flowmeter (HRF) flow images by recording flow measurements from specific regions of the retinal vasculature in in-vitro and in-vivo eye models in which retinal blood flow can be manipulated. Methods: The first experiments utilised an isolated perfused pig eyes perfused with a 50%/50% Krebs/RBC solution at known flow rates ranging from zero to 300 μl/min. After HRF image acquisition, the retinal vasculature was perfused with fluorescein isothiocyanate (FITC), for fluorescence microscopy. Using the standard HRF software and a 10×10 pixel measurement window, flow rates were measured from a retinal artery, vein, arteriole, venule, and the retinal capillary bed and a capillary-free-zone. The relationship between HRF measured flow and perfusion flow in the different measurement regions was determined. For the second study, HRF flow images were acquired at retinal sites in Brown Norway rats over a range of focus levels before and after cessation of retinal blood flow by laser-induced central retinal artery occlusion. Using the 10×10 pixel and 4×4 pixel measurement windows, HRF measured flow was performed in retinal artery, vein, arteriole, capillary and choroidal vessel locations. The relationship between HRF measured flow and focus depth was determined for each location before and after central retinal artery occlusion. At the conclusion of each experiment the effect of reduction of systemic blood pressure (by exsanguination) on HRF flow measurements in choroidal vessels and in locations without visible choroidal vessels was assessed. Finally, HRF flow measurements were acquired after euthanasia, to determine the HRF flow signal which was still present under zero biological flow conditions (the zerooffset). Results: In the isolated perfused pig eye experiments it was found that the HRF flow response varied according to vascular location. At zero perfusate flow, HRF flow was consistently greater than zero at all locations, averaging 171.9 ± 44.7 AU (n=97), representing background noise. Arteries and veins yielded the highest HRF measured flow values, but the relationship between HRF measured flow and perfusate flow was not linear. In arterioles the HRF flow was more linear over a broader range of perfusate flow rates but the peak flow signal was an order of magnitude smaller than that in arteries and veins. Both the linearity and magnitude of the flow signal in venules was less than that in arterioles.

O sinal de fluxo cutâneo obtido via fluxometria Laser Doppler (SFLD) tem flutuações de baixas frequências que estão relacionadas a mecanismos de controle do fluxo microvascular. Análises espectrais, via transformada de Fourier e transformada de wavelet, têm sido usadas para correlacionar as flutuações de SFLD com os seguintes mecanismos de controle de fluxo: metabólico, metabólico NO-dependente, neurogênico e miogênico, nos respectivos intervalos de frequência 0,005-0,0095 Hz, 0,0095-0,02 Hz, 0,02-0,05 Hz e 0,05-0,15 Hz. A potência do sinal, em cada intervalo de frequência, geralmente é usada como uma medida da atividade do mecanismo de controle microvascular relacionado. Uma vez que os métodos usados de análise são espectrais, as características das flutuações do SFLD, em cada intervalo de frequência, no domínio do tempo são desconhecidas. Como consequência, há ausência de critérios objetivos para medir adequadamente, em cada intervalo de frequência, os parâmetros hemodinâmicos relacionados. O objetivo deste trabalho foi caracterizar e quantificar flutuações temporais, espaciais e espaço-temporais do SFLD em cada faixa de frequência, usando um método no domínio do tempo. Os fluxos basais (320C) e termicamente estimulados à (420C) das regiões volares de antebraços de 20 voluntários saudáveis foram coletados em duas regiões próximas e analisados. As análises dos dados obtidos indicam que janelas temporais pequenas (1 minuto) são aceitáveis para a quantificação do fluxo médio, e que janelas temporais maiores são necessários para quantificar as flutuações de fluxo. A análise espaço-temporal revelou uma forte correlação entre sinais (em todas as bandas, exceto na banda B5) das duas regiões investigadas, durante longos intervalos de tempo, quando as duas regiões estudadas foram termicamente estimuladas, e menor variabilidade intragrupo quando comparada à obtida para os valores médios das flutuações, sugerindo que o intervalo de tempo de correlação é um parâmetro promissor para estudar mecanismos de controle do fluxo microvascular. / The laser Doppler flow signal from the skin (LDFS) has low-frequency fluctuations which are related to microvascular mechanisms of flow control. The Fourier and the wavelet spectral analysis has been used to correlate fluctuations in the LDFS with the metabolic, metabolic NO-dependent, neurogenic and myogenic mechanisms of control in the frequency intervals 0.005-0.0095 Hz, 0.0095-0.02 Hz, 0.02-0.05 Hz and 0.05-0.15 Hz, respectively. The signal power, in each frequency interval, is generally used as a measure of the activity of the related mechanism of microvascular control. Since spectral analysis methods have been used, the time-domain characteristics of the fluctuations in the LDFS in each frequency interval are unknown. As a consequence, there is a lack of objective criteria to properly measure, in each frequency interval, the related hemodynamic parameters. The aim of this work was characterizing and quantifying temporal, spatial and spatial-temporal fluctuations in the LDFS in each frequency band, using a time-domain method. Baseline (320C) and thermally stimulated (420C) LDFS of volar forearms from 20 healthy volunteers were collected from two close regions and analyzed. The data obtained indicate that short-time windows (1 minute) are acceptable for quantifying the mean flow, and that larger time-windows are needed for quantifying the flow fluctuations. The spatialtemporal analysis revealed strong correlations between signals (all bands, except B5) from the two investigated regions, during large time intervals when thermally stimulated, and lower intragroup variability than the ones obtained for the mean values of fluctuations, suggesting that the time interval of correlation is a promising parameter for studying mechanisms of microvascular flow control.

A quimioterapia e a radioterapia são modalidades terapêuticas não cirúrgicas aplicadas a pacientes com neoplasias malignas. A mucosite oral (MO) é uma inflamação da mucosa oral decorrente destas terapias antineoplásicas, manifestando-se por atrofia, inchaço, eritema e úlcera, comprometendo a qualidade de vida. A patogênese da mucosite oral envolve uma cascata de eventos de natureza inflamatória que culminam em alterações no epitélio e no tecido conjuntivo. Dentre estas modificações destacam-se as alterações na microvascularização, as quais precedem as alterações epiteliais na mucosa oral induzida por radiação e pelos agentes quimioterápicos. A Fluxometria Laser Doppler é um método não invasivo que permite avaliar parâmetros clínicos da microcirculação através do monitoramento do fluxo continuamente, em tempo real. O objetivo deste estudo foi avaliar a fluxo sanguíneo na região geniana em pacientes sob radioterapia de cabeça e pescoço ou quimioterapia através da técnica de Fluxometria Laser Doppler e comparar a graduação de mucosite oral e dor com dados obtidos na avaliação do fluxo sanguíneo. Este estudo observacional e prospectivo teve uma amostra de 14 pacientes oncológicos que foram avaliados antes do início da terapia antineoplásica e durante a fase intensiva da radioterapia de cabeça e pescoço ou quimioterapia, em 7 momentos. Para esta avaliação foi utilizado o Fluxômetro Laser Doppler para o registro do fluxo sanguíneo; as escalas da OMS (Organização Mundial da Saúde) e OMAS (Oral Mucositis Assessment Scale) para a avaliação do grau de mucosite; e Escala Visual Analógica (EVA) para a avaliação da dor em mucosa oral. Ao se comparar o fluxo sanguíneo nos tempos T1, T2, T3, T4, T5 e T6 com o T0, para os pacientes submetidos a radioterapia de cabeça e pescoço, não houve diferença estatística (p>0,05). Para os pacientes sob quimioterapia, houve diferença estatística nos tempo T1 (p=0,033) e T6 (p=0,043). Houve correlação positiva fraca entre as escalas para avaliação de mucosite oral (OMS (p=0,031) e OMAS (p=0,009)) e o fluxo sanguíneo. Não houve grau de relação entre dor induzida por mucosite oral e fluxo sanguíneo (p>0,05). A Fluxometria Laser Doppler permitiu a observação da dinâmica microvascular da região geniana da face em pacientes sob terapia antineoplásica e com risco de desenvolvimento de mucosite oral. Nos pacientes sob quimioterapia, houve aumento de perfusão cutânea na face nos tempos iniciais da MO, com progressiva redução do fluxo no decorrer do ciclo de quimioterapia. / Chemotherapy and radiotherapy are non surgical therapeutic modalities to malignancies. Oral mucositis is a inflammation of the oral mucosa due to these cancer therapy, typically manifesting as atrophy, swelling, erythema and ulceration compromising the quality of life. The pathogenesis of oral mucositis (OM) involves a cascade of inflammation events that result in changes in the epithelial layer and connective tissue, including microvascular modifications. These modifications precede epithelial changes induced by radiation therapy and chemotherapeutic agents, thereby modifications in blood flow may be a predictive factor of the severity of oral mucositis. Laser Doppler flowmetry (LDF) is a non invasive method enabling the monitoring of microvascular blood flow continuously in real time. The aim of this study was to evaluate the blood flow in the genius region in patients undergoing head and neck radiation and/or chemotherapy by Laser Doppler Flowmetry and compare the degree of oral mucositis and pain with data obtained in the evaluation of blood flow. This prospective observational study had a sample of 14 oncologic patients who were evaluated before and during the intensive phase of head and neck radiotherapy or chemotherapy in 7 times. For this evaluation, we used the Laser Doppler Flowmeter to measure blood flow; WHO scale (World Health Organization) and OMAS (Oral Mucositis Assessment Scale) for assessing the severity of mucositis; and Visual Analogue Scale (VAS) for pain assessment in oral mucosa. When we compare blood flow in T1, T2, T3,T4, T5 and T6 with T0, for patients undergoing radiotherapy for head and neck, there was no statistical difference (p> 0.05). For patients undergoing chemotherapy, there was a statistical difference in time T1 (p = 0.033) and T6 (p = 0.043). There was a weak positive correlation between the scale for assessing oral mucositis (WHO (p = 0.031) and OMAS (p = 0.009)) and blood flow. There was no relation degree pain induced oral mucositis and blood flow (p>0.05). Laser Doppler flowmetry allowed the observation of microvascular dynamics in the genian region of the face in patients undergoing antineoplastic therapy and risk of developing mucositis. In patients undergoing chemotherapy, there was an increase of skin perfusion in the face in the early days of the OM, with progressive reduction in flow during the course of chemotherapy.

This report documents the measurements of turbulence quantities resulting from vortices embedded in a zero pressure gradient turbulent boundary layer. Turbulent boundary layers are found in most flow regimes over large scale vehicles and have been studied for many years. Various systems to control separation of boundary layers have been proposed, but vortex generators have proven to be an economical choice as they are often used to fix deficiencies in a flow field after large scale production of a vehicle has commenced. In order to better understand the interaction between vortex generators and the boundary layer in which they are embedded, an experiment has been performed using through non-invasive Comprehensive Laser Doppler Velocimeter. The results show that normalization on edge velocity is appropriate for comparison with previous work. The 1/S parameter and vq^2 parameter were found to be most appropriate to correlate the Reynolds stresses and triple products, respectively. The higher inflow edge velocity and greater momentum thickness, creating a lower vortex generator to boundary layer height ratio, result in a more diffuse vortex as compared to previous work conducted in the same wind tunnel, with the same geometry, but with different inflow conditions. / Master of Science

It is recognized that detailed knowledge of turbulence parameters, as well as velocities, can aid in understanding and modeling mixing rate-dominated phenomena in stirred vessels. Measurements using a laser-Doppler velocimeter and modeling using a k-ε turbulence model and FLUENT, a general-purpose fluid flow modeling program, have been conducted of the flow in a baffled, turbine-agitated vessel. The complex flow patterns and high turbulence intensities explain why flows in stirred vessels are difficult to attack experimentally or numerically. In the measurements, the necessary corrections for the periodic, nondissipative velocity fluctuations in the near-impeller region, which were caused by the periodic passage of the impeller blades, were made by an autocorrelation method. With the contributions of the periodic fluctuations removed, meaningful turbulence data including turbulence intensities, autocorrelation functions, turbulence energy spectra, turbulence scales, and turbulence energy dissipation rates were obtained. Integral scales and energy dissipation rates were a particular objective in this work because of their usefulness in modeling local mixing rates in turbulent flows. An energy balance around a region containing the impeller and the impeller stream showed that 60% of the energy transmitted into the vessel via the impeller was dissipated in the region, and 40% was dissipated in the rest of the vessel. An equation for calculating local energy dissipation rates ε from total turbulence energy and resultant integral scales, ε = A q³/² /L(res), appeared adequate with constant A = 0.85 (where q ≡ uᵢuᵢ/2, L(res) ≡√LᵢLᵢ, and uᵢ and Lᵢ are, respectively, the i-th component of fluctuation velocity and the turbulence integral scale measured in direction i). Both the k-ε model (two-dimensional) and FLUENT (which employed three-dimensional k-ε and Reynolds stress models) obtained mean velocity profiles fairly close to the experimental data, but both predicted k and ε significantly lower than the measured values. The reason for the underestimation of k and ε was not entirely clear, but may have been caused by use of only the random parts of velocities for computing k and ε at the impeller boundary. The objective of modeling complex turbulent flows in stirred vessels has been accomplished, a goal which until recently would have been considered beyond the possibility of computation.

People with diabetes suffer from a high risk of developing foot related diseases. It is therefore important to perform a blood pressure measurement on the toe to be able to diagnose and treat in time. Using laser Doppler flowmetry has been proven to be a useful technique for this purpose during a standard blood pressure measurement procedure using a cuff. The laser Doppler probe detects once the blood flow returns which can then be related to the pressure value. However, the algorithm currently used by the company for detection of return of blood flow is in need of improvements. This thesis aims to develop an improved algorithm, which is more robust against artifacts. Furthermore, a warning system for uncertainties in the detection will be developed and integrated with the new algorithm. To create the algorithm an investigation of the signals’ appearances was performed to obtain an understanding of what artifacts and characteristics the algorithm should be able to handle. First three different basic approaches were implemented and tested, namely model curve, threshold and pulsations. These algorithms were then combined into two different more complex algorithms. One of them consisted of the model curve and the pulsation algorithm, the second combined algorithm consisted of the threshold algorithm and the pulsation algorithm. From the result it was found that the second combined algorithm performed best. It had a high accuracy and a well-functioning warning system. However, the algorithm had problems to correctly detect the return of flow when it is characterised by a slow increase of the perfusion. The biggest contribution by this thesis is the newly developed warning system. A false detection can lead to a false diagnose to be given if the operator is not attentive. The warning system is therefore an important feature since it can prevent this from occurring.

<p>Under 20 års tid har Perimed AB utvecklat och tillverkat LDPM- och LDPI-instrument som är baserade på en analog filterkonstruktion. De analoga komponenterna i konstruktionen är komplexa och icke-linjära med hänsyn till frekvens och de driver även med temperaturen. Funktionen hos konstruktionen beror också kraftigt av att de analoga komponenterna trimmas in under produktionen.</p><p>Det här examensarbetet syftar till att ta fram en alternativ design baserad kring en digital signal processor. Den digitala signalbehandlingsmetod som beskrivs baseras på väl förankrade laser-Doppler perfusionsteorier. Den implementerade signalbehandlingsalgoritmen beräknar perfusionen ur en samplad fotodetektorström, som har filtrerats till AC- och DC-komponenter med hjälp av ett analogt detektorkort. Algoritmen producerar en råperfusionssignal genom att beräkna en frekvensviktad summa av fotodetektorströmmens effektspektrum. Kompensation för detektorns brus och normalisering med ljusintensitet har också implementerats.</p><p>Den presenterade implementationen har verifierats mot ett exemplar av LDPM-enheten PF 5010 som har använts som referensinstrument vid alla mätningar. Mätningar in vitro har påvisat liknande mätresultat som referensinstrumentet för en referensvätska med hög perfusion och även för ett statiskt mätobjekt. Vidare har implementationen verifierats med mätningar in vivo på hud, vilket har påvisat nära nog identiska signalnivåer och gensvar på värmeprovokationer som referensinstrumentet.</p><p>Den demonstrerade uppfinningen förenklar tillverkningen av instrumenten eftersom antalet komponenter reduceras avsevärt och därmed antalet produktionstester. Användandet av en DSP reducerar dessutom instrumentets temperaturkänslighet eftersom den ersätter flera temperaturkänsliga komponenter.</p> / <p>For 20 years Perimed AB have been developing and manufacturing LDPM and LDPI instruments based on an analog filter construction. The analog components in the construction are complex and suffer from non-linear frequency dependency and temperature drifts. The functionality of the design is also heavily depending on analog components which need to be trimmed in the production.</p><p>In this thesis, an alternative design employing a digital signal processor is presented. The signal processing method used is based on well established laser Doppler perfusion theories. The implemented signal processing algorithm calculates the perfusion from a sampled photodetector current, pre-filtered into AC and DC components by an analog detector card. The algorithm produces a raw perfusion signal by calculating a frequency weighted sum of the power spectral density, PSD, of the photocurrent. Detector noise compensation and light intensity normalization of the signal has also been implemented.</p><p>The presented digital implementation has been verified using the PF 5010 LDPM unit as a reference. In vitro measurements have shown similar behaviour as the reference in a highly perfused reference fluid as well as for a static scatterer. Furthermore, the DSP implementation has been verified on in vivo measurements of skin, showing nearly identical signal levels and response to heat provocation as the reference.</p><p>The demonstrated invention improves the manufacturability of the instruments since it reduces the number of electronic components significantly and thus, the amount of manufacturing tests. The DSP also reduces the temperature sensitivity of the instrument since it replaces several analog components sensitive to temperature changes.</p>

La thèse porte sur l'étude de la convection capillaire (effet Marangoni) et son couplage avec la convection thermogravitationnelle. Le travail met en oeuvre des mesures de champ de vitesse par vélocimétrie laser, d'une part, et des simulations numériques de ces expériences, d'autre part. Des solutions asymptotiques sont également utilisées, et la transition de la convection stationnaire vers un état d'oscillations spatiales ou spatio-temporelles a été analysée. Le manuscript aborde également des situations impliquant l'effet de thermodiffusion, ainsi que les mouvements dans une bicouche de fluides immiscibles.

Under 20 års tid har Perimed AB utvecklat och tillverkat LDPM- och LDPI-instrument som är baserade på en analog filterkonstruktion. De analoga komponenterna i konstruktionen är komplexa och icke-linjära med hänsyn till frekvens och de driver även med temperaturen. Funktionen hos konstruktionen beror också kraftigt av att de analoga komponenterna trimmas in under produktionen. Det här examensarbetet syftar till att ta fram en alternativ design baserad kring en digital signal processor. Den digitala signalbehandlingsmetod som beskrivs baseras på väl förankrade laser-Doppler perfusionsteorier. Den implementerade signalbehandlingsalgoritmen beräknar perfusionen ur en samplad fotodetektorström, som har filtrerats till AC- och DC-komponenter med hjälp av ett analogt detektorkort. Algoritmen producerar en råperfusionssignal genom att beräkna en frekvensviktad summa av fotodetektorströmmens effektspektrum. Kompensation för detektorns brus och normalisering med ljusintensitet har också implementerats. Den presenterade implementationen har verifierats mot ett exemplar av LDPM-enheten PF 5010 som har använts som referensinstrument vid alla mätningar. Mätningar in vitro har påvisat liknande mätresultat som referensinstrumentet för en referensvätska med hög perfusion och även för ett statiskt mätobjekt. Vidare har implementationen verifierats med mätningar in vivo på hud, vilket har påvisat nära nog identiska signalnivåer och gensvar på värmeprovokationer som referensinstrumentet. Den demonstrerade uppfinningen förenklar tillverkningen av instrumenten eftersom antalet komponenter reduceras avsevärt och därmed antalet produktionstester. Användandet av en DSP reducerar dessutom instrumentets temperaturkänslighet eftersom den ersätter flera temperaturkänsliga komponenter. / For 20 years Perimed AB have been developing and manufacturing LDPM and LDPI instruments based on an analog filter construction. The analog components in the construction are complex and suffer from non-linear frequency dependency and temperature drifts. The functionality of the design is also heavily depending on analog components which need to be trimmed in the production. In this thesis, an alternative design employing a digital signal processor is presented. The signal processing method used is based on well established laser Doppler perfusion theories. The implemented signal processing algorithm calculates the perfusion from a sampled photodetector current, pre-filtered into AC and DC components by an analog detector card. The algorithm produces a raw perfusion signal by calculating a frequency weighted sum of the power spectral density, PSD, of the photocurrent. Detector noise compensation and light intensity normalization of the signal has also been implemented. The presented digital implementation has been verified using the PF 5010 LDPM unit as a reference. In vitro measurements have shown similar behaviour as the reference in a highly perfused reference fluid as well as for a static scatterer. Furthermore, the DSP implementation has been verified on in vivo measurements of skin, showing nearly identical signal levels and response to heat provocation as the reference. The demonstrated invention improves the manufacturability of the instruments since it reduces the number of electronic components significantly and thus, the amount of manufacturing tests. The DSP also reduces the temperature sensitivity of the instrument since it replaces several analog components sensitive to temperature changes.

Thèse de doctorat : sciences. Thermique et énergétique : Toulouse, ONERA : 2002. Thèse de doctorat : sciences. Thermique et énergétique : Ecully, Ecole centrale de Lyon : 2002. / 220 réf.