Physiological and pathological human ocular perfusion characteristics

There were three principle aims to this thesis. Firstly, the acquisition protocols of clinical blood flow apparatus were investigated in order to optimise them for both cross-sectional and longitudinal application. Secondly, the effects of physiological factors including age and systematic circulation on ocular blood flow were investigated. Finally, the ocular perfusion characteristics of patients diagnosed with ocular diseases considered to be of a vascular origin were investigated. The principle findings of this work are:- 1) Optimisation of clinical investigationsPhotodiode sensitivity of the scanning laser Doppler flowmeter should be kept within a range of 70-150 DC when acquiring images of the retina and optic nerve head in order to optimise the reproducibility of capillary blood flow measures. Account of the physiological spatial variation in retinal blood flow measures can be made using standard analysis protocols of the scanning laser Doppler flowmeter combined with a local search strategy. Measurements of pulsatile ocular blood flow using the ocular blood flow analyser are reproducible, however this reproducibility can be improved when consecutive intraocular pressure pulses are used to calculate pulsatile ocular blood flow. Spectral analysis of the intraocular pressure pulse-wave is viable and identifies the first four harmonic components of the waveform. 2) Physiological variation in ocular perfusionAge results in a significant reduction in perfusion of the retinal microcirculation, which is not evident in larger vessel beds such as the choroid. Despite known asymmetry in the systemic vasculature, no evidence of interocular asymmetry in ocular perfusion is apparent. 3) Pathological variation in ocular perfusionIn primary open angle glaucoma, perfusion is reduced in the retinal microcirculation of patients classified as having early to moderate visual field defects. However, ocular pulsatility defects are masked when patients and subjects are matched for systemic variables (pulse rate and mean arterial pressure); differentiation is facilitated by the application of waveform analysis to the continuos intraocular pressure curve even in the early stages of disease. Diabetic patients with adequate glycaemic control, exhibit maintenance of macular blood flow, macular topography and visual function following phacoemulsification.

Hydrodynamic phenomena in the downcomer during flow rate transients in the primary circuit of a PWR

Mixing phenomena observed when the flow rate in a single loop of the primary circuit is changed can influence the operation of pressurized water reactor (PWR) by inducing local gradients of boron concentration or coolant temperature. Analysis of one-dimensional Laser Doppler Anemometry (LDA) measurements during the start-up and shutdown of pump on a single loop of the ROCOM test facility has been performed. The effect of a step change and a ramped change in the flow rate on the axial and azimuthal velocities was examined. Numerical simulations were also performed for the step change in the flow rate that gave quantitative agreement with the axial velocities. Phenomenological agreement was made on the turbulent kinetic energy; however, observed values were a factor of 2.5 less than the turbulent kinetic energy derived from the measurements. © 2007.

Effects of short-term detraining on postprandial metabolism, endothelial function, and inflammation in endurance-trained men:dissociation between changes in triglyceride metabolism and endothelial function

Endurance-trained athletes experience a low level of postprandial lipaemia, but this rapidly increases with detraining. We sought to determine whether detraining-induced changes to postprandial metabolism influenced endothelial function and inflammation. Eight endurance-trained men each undertook two oral fat tolerance tests [blood taken fasted and for 6 h following a high-fat test meal (80 g fat, 80 g carbohydrate)]: one during a period of their normal training (trained) and one after 1 wk of no exercise (detrained). Endothelial function in the cutaneous microcirculation was assessed using laser Doppler imaging with iontophoresis in the fasted state and 4 h postprandially during each test. Fasting plasma triglyceride (TG) concentrations increased by 35% with detraining (P = 0.002), as did postprandial plasma (by 53%, P = 0.002), chylomicron (by 68%, P = 0.02) and very low-density lipoprotein (by 51%, P = 0.005) TG concentrations. Endothelial function decreased postprandially in both the trained (by 17%, P = 0.03) and detrained (by 22%, P = 0.03) conditions but did not differ significantly between the trained and detrained conditions in either the fasted or the postprandial states. These results suggest that, although fat ingestion induces endothelial dysfunction, interventions that alter postprandial TG metabolism will not necessarily concomitantly influence endothelial function.

Regional variation in peripapillary retinal blood flow in primary open angle glaucoma:a follow-up study

Purpose: To investigate whether regional long-term changes in peripapillary retinal flow, measured by scanning laser Doppler flowmetry (SLDF), occur in patients with primary open angle glaucoma (POAG). Methods: 31 healthy volunteers (mean age: 65 8.3 years) and 33 POAG patients (mean age: 71.2 7.6 years) were followed up every 4 months for 16 months. Using SLDF, three images of the superior and inferior optic nerve head were obtained for each subject. A 1010-pixel frame was used to measure blood flow, volume and velocity in the four quadrants of the peripapillary retina. Central 24-2 visual field testing was carried out at each visit. Repeated measures analysis of covariance was used to assess change over time between the normal and POAG groups for the SLDF parameters. Univariate linear regression analysis for mean deviation and glaucoma change probability (GCP) analysis were used to identify visual field progression. Results: Blood volume, flow and velocity measured in the inferior nasal quadrant of the peripapillary retina decreased significantly over time for the POAG group compared to the normal group (p=0.0073, 0.0097, 0.0095 respectively). Overall, 2 glaucoma patients showed a significantly deteriorating MD slope, while 7 patients showed visual field progression with GPA. All of the patients progressing with GPA, showed change in the superior hemifield and, of those, 14% showed change in the inferior hemifield. Conclusion: Glaucoma patients showed a decrease in blood flow, volume and velocity in the inferior nasal peripapillary retina. A regional variation in microvascular retinal capillary blood flow may provide insight into the pathogenesis of glaucomatous optic neuropathy. Keywords: 331 blood supply • 554 retina • 624 visual fields

Abnormal systemic and ocular vascular response to temperature provocation in primary open-angle glaucoma patients:a case for autonomic failure?

PURPOSE. To assess systemic and ocular vascular reactivity in response to warm and cold provocation in untreated patients with primary open-angle glaucoma and normal control subjects. METHODS. Twenty-four patients with primary open-angle glaucoma and 22 normal control subjects were subjected to a modified cold pressor test involving immersion of the right hand in 40°C warm water followed by 4°C cold water exposure, and finger and ocular blood flow were assessed by means of peripheral laser Doppler flowmetry and retinal flowmetry, respectively. Finger and body temperature as well as intraocular pressure, systemic blood pressure, systemic pulse pressure, heart rate, and ocular perfusion pressure were also monitored. RESULTS. The patients with glaucoma demonstrated an increase in diastolic blood pressure (P = 0.023), heart rate (P = 0.010), and mean ocular perfusion pressure (P = 0.039) during immersion of the tested hand in 40°C water. During cold provocation, the patients demonstrated a significant decrease in finger (P = 0.0003) and ocular blood flow (the parameter velocity measured at the temporal neuroretinal rim area; P = 0.021). Normal subjects did not demonstrate any blood flow or finger temperature changes during immersion of the tested hand in 40°C water (P > 0.05); however, they exhibited increases in systolic blood pressure (P = 0.034) and pulse pressure (P = 0.0009) and a decrease in finger blood flow (P = 0.0001) during cold provocation. In normal subjects, the ocular blood flow was unchanged during high- and low-temperature challenge. CONCLUSIONS. Cold provocation elicits a different blood pressure, and ocular blood flow response in patients with primary open-angle glaucoma compared with control subjects. These findings suggest a systemic autonomic failure and ocular vascular dysregulation in POAG patients.

The blood perfusion and NADH/FAD content combined analysis in patients with diabetes foot

Skin blood microcirculation and the metabolism activity of tissue were examined on the patients with type 2 diabetes. Laser Doppler flowmetry (LDF) with 1064 nm laser light source and fluorescence spectroscopy (FS) with excitation light of 365 nm and 450 nm have been used to monitor the blood perfusion and the content of coenzymes NADH and FAD. Concluding, the proposed combined LDF and tissue FS approach allows to identify the significant violations in the blood microcirculation and metabolic activity for type 2 diabetes patients.

The development of attenuation compensation models of fluorescence spectroscopy signals

This study examines the effect of blood absorption on the endogenous fluorescence signal intensity of biological tissues. Experimental studies were conducted to identify these effects. To register the fluorescence intensity, the fluorescence spectroscopy method was employed. The intensity of the blood flow was measured by laser Doppler flowmetry. We proposed one possible implementation of the Monte Carlo method for the theoretical analysis of the effect of blood on the fluorescence signals. The simulation is constructed as a four-layer skin optical model based on the known optical parameters of the skin with different levels of blood supply. With the help of the simulation, we demonstrate how the level of blood supply can affect the appearance of the fluorescence spectra. In addition, to describe the properties of biological tissue, which may affect the fluorescence spectra, we turned to the method of diffuse reflectance spectroscopy (DRS). Using the spectral data provided by the DRS, the tissue attenuation effect can be extracted and used to correct the fluorescence spectra.

Leukotriene B⁴ and platelet-activating factor : assessment of biological significance in neutrophil trafficking

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Blue flicker modifies the subfoveal choroidal blood flow in the human eye

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Piezoelectric energy harvesting using blood-flow-like excitation for implantable devices

The goal of this research is to produce a system for powering medical implants to increase the lifetime of the implanted devices and reduce the battery size. The system consists of a number of elements – the piezoelectric material for generating power, the device design, the circuit for rectification and energy storage. The piezoelectric material is analysed and a process for producing a repeatable high quality piezoelectric material is described. A full width half maximum (FWHM) of the rocking curve X-Ray diffraction (XRD) scan of between ~1.5° to ~1.7° for test wafers was achieved. This is state of the art for AlN on silicon and means devices with good piezoelectric constants can be fabricated. Finite element modelling FEM) was used to design the structures for energy harvesting. The models developed in this work were established to have an accuracy better than 5% in terms of the difference between measured and modelled results. Devices made from this material were analysed for power harvesting ability as well as the effect that they have on the flow of liquid which is an important consideration for implantable devices. The FEM results are compared to experimental results from laser Doppler vibrometry (LDV), magnetic shaker and perfusion machine tests. The rectifying circuitry for the energy harvester was also investigated. The final solution uses multiple devices to provide the power to augment the battery and so this was a key feature to be considered. Many circuits were examined and a solution based on a fully autonomous circuit was advanced. This circuit was analysed for use with multiple low power inputs similar to the results from previous investigations into the energy harvesting devices. Polymer materials were also studied for use as a substitute for the piezoelectric material as well as the substrate because silicon is more brittle.

Leukotriene B⁴ and platelet-activating factor : assessment of biological significance in neutrophil trafficking

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Blue flicker modifies the subfoveal choroidal blood flow in the human eye

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Tailoring Magnetic, Mechanical and Dielectric Properties of Magnetorheological Elastomers based on Natural Rubber and Iron by Magnetic Field Assisted Curing for Possible Applications

If magnetism is universal in nature, magnetic materials are ubiquitous. A life without magnetism is unthinkable and a day without the influence of a magnetic material is unimaginable. They find innumerable applications in the form of many passive and active devices namely, compass, electric motor, generator, microphone, loud speaker, maglev train, magnetic resonance imaging, data recording and reading, hadron collider etc. The list is endless. Such is the influence of magnetism and magnetic materials in ones day to day life. With the advent of nanoscience and nanotechnology, along with the emergence of new areas/fields such as spintronics, multiferroics and magnetic refrigeration, the importance of magnetism is ever increasing and attracting the attention of researchers worldwide. The search for a fluid which exhibits magnetism has been on for quite some time. However nature has not bestowed us with a magnetic fluid and hence it has been the dream of many researchers to synthesize a magnetic fluid which is thought to revolutionize many applications based on magnetism. The discovery of a magnetic fluid by Jacob Rabinow in the year 1952 paved the way for a new branch of Physics/Engineering which later became magnetic fluids. This gave birth to a new class of material called magnetorheological materials. Magnetorheological materials are considered superior to electrorheological materials in that magnetorheology is a contactless operation and often inexpensive.Most of the studies in the past on magnetorheological materials were based on magnetic fluids. Recently the focus has been on the solid state analogue of magnetic fluids which are called Magnetorheological Elastomers (MREs). The very word magnetorheological elastomer implies that the rheological properties of these materials can be altered by the influence of an external applied magnetic field and this process is reversible. If the application of an external magnetic field modifies the viscosity of a magnetic fluid, the effect of external magnetic stimuli on a magnetorheological elastomer is in the modification of its stiffness. They are reversible too. Magnetorheological materials exhibit variable stiffness and find applications in adaptive structures of aerospace, automotive civil and electrical engineering applications. The major advantage of MRE is that the particles are not able to settle with time and hence there is no need of a vessel to hold it. The possibility of hazardous waste leakage is no more with a solid MRE. Moreover, the particles in a solid MRE will not affect the performance and durability of the equipment. Usually MR solids work only in the pre yield region while MR fluids, typically work in the post yield state. The application of an external magnetic field modifies the stiffness constant, shear modulus and loss modulus which are complex quantities. In viscoelastic materials a part of the input energy is stored and released during each cycle and a part is dissipated as heat. The storage modulus G′ represents the capacity of the material to store energy of deformation, which contribute to material stiffness. The loss modulusG′′ represents the ability of the material to dissipate the energy of deformation. Such materials can find applications in the form of adaptive vibration absorbers (ATVAs), stiffness tunable mounts and variable impedance surfaces. MREs are an important material for automobile giants and became the focus of this research for eventual automatic vibration control, sound isolation, brakes, clutches and suspension systems

Microcantilever sensors for biochemical detection and analysis

Biochemical agents, including bacteria and toxins, are potentially dangerous and responsible for a wide variety of diseases. Reliable detection and characterization of small samples is necessary in order to reduce and eliminate their harmful consequences. Microcantilever sensors offer a potential alternative to the state of the art due to their small size, fast response time, and the ability to operate in air and liquid environments. At present, there are several technology limitations that inhibit application of microcantilever to biochemical detection and analysis, including difficulties in conducting temperature-sensitive experiments, material inadequacy resulting in insufficient cell capture, and poor selectivity of multiple analytes. This work aims to address several of these issues by introducing microcantilevers having integrated thermal functionality and by introducing nanocrystalline diamond as new material for microcantilevers. Microcantilevers are designed, fabricated, characterized, and used for capture and detection of cells and bacteria. The first microcantilever type described in this work is a silicon cantilever having highly uniform in-plane temperature distribution. The goal is to have 100 μm square uniformly heated area that can be used for thermal characterization of films as well as to conduct chemical reactions with small amounts of material. Fabricated cantilevers can reach above 300C while maintaining temperature uniformity of 2−4%. This is an improvement of over one order of magnitude over currently available cantilevers. The second microcantilever type is a doped single crystal silicon cantilever having a thin coating of ultrananocrystalline diamond (UNCD). The primary application of such a device is in biological testing, where diamond acts as a stable, electrically isolated reaction surface while silicon layer provides controlled heating with minimum variations in temperature. This work shows that composite cantilevers of this kind are an effective platform for temperature-sensitive biological experiments, such as heat lysing and polymerase chain reaction. The rapid heat-transfer of Si-UNCD cantilever compromised the membrane of NIH 3T3 fibroblast and lysed the cell nucleus within 30 seconds. Bacteria cells, Listeria monocytogenes V7, were shown to be captured with biotinylated heat-shock protein on UNCD surface and 90% of all viable cells exhibit membrane porosity due to high heat in 15 seconds. Lastly, a sensor made solely from UNCD diamond is fabricated with the intention of being used to detect the presence of biological species by means of an integrated piezoresistor or through frequency change monitoring. Since UNCD diamond has not been previously used in piezoresistive applications, temperature-denpendent piezoresistive coefficients and gage factors are determined first. The doped UNCD exhibits a significant piezoresistive effect with gauge factor of 7.53±0.32 and a piezoresistive coefficient of 8.12×10^−12 Pa^−1 at room temperature. The piezoresistive properties of UNCD are constant over the temperature range of 25−200C. 300 μm long cantilevers have the highest sensitivity of 0.186 m-Ohm/Ohm per μm of cantilever end deflection, which is approximately half that of similarly sized silicon cantilevers. UNCD cantilever arrays were fabricated consisting of four sixteen-cantilever arrays of length 20–90 μm in addition to an eight-cantilever array of length 120 μm. Laser doppler vibrometry (LDV) measured the cantilever resonant frequency, which ranged as 218 kHz−5.14 MHz in air and 73 kHz−3.68 MHz in water. The quality factor of the cantilever was 47−151 in air and 18−45 in water. The ability to measure frequencies of the cantilever arrays opens the possibility for detection of individual bacteria by monitoring frequency shift after cell capture.

Étude expérimentale de l'écoulement en entrée d'aspirateur d'une turbine bulbe

Ce mémoire présente l’étude expérimentale de l’écoulement d’entrée d’un aspirateur d’une turbine bulbe présentant une chute abrupte de performance. Des mesures par vélocimétrie laser à effet Doppler (LDV) ont été réalisées sur deux axes soit en aval des pales de la roue et en aval du moyeu de la roue. Une particularité de cette étude est la conception d’un montage permettant de mesurer la vitesse axiale proche de la paroi du cône. De plus, une méthode d’estimation de la vitesse radiale moyenne a été développée. Ces mesures ont permis de caractériser l’écoulement primaire et les écoulements secondaires et d’analyser leur évolution entre les deux axes. De plus, l’évolution de ces écoulements est analysée en fonction de la chute de performance de la turbine. Les principales particularités de l’écoulement sont la présence d’une recirculation sous le moyeu, d’une zone contrarotative, des sillages des directrices et des tourbillons de bout de pale.