The phase-encoded method of NMR flow imaging is examined in detail. The motion of isochromatic groups in the direction of suitably balanced magnetic field gradients will give a phase change in the NMR signal directly proportional to the velocity, acceleration, or higher derivative of position, dependent upon the form of the field gradient. If a simple bipolar pulse is used then the phase change, for isochromats moving with constant velocity, will be proportional to the velocity. If two such pulses are placed back to back then the phase change is proportional to the acceleration. The motion of isochromats in the magnetic field gradients used for imaging will also cause phase changes. These effects are considered, and simple methods of reducing them presented. Phase errors due to main field inhomogeneity are shown to be eliminated by a simple phase difference technique. In this two image data sets having different flow sensitivities are obtained, and the phase difference between them calculated. Velocity images were obtained using this technique, both by the manipulation of the frequency-encoding and selection gradients, and by the insertion of bipolar pulses in the imaging sequence. Acceleration images were also produced by adding double bipolar pulses to the imaging sequence. Both spin-echo and field-echo sequences were used. Field-echo sequences were shown to be superior for high velocities, particularly when the direction of flow is through the slice, otherwise spin-echo sequences were preferred. The Fourier imaging of velocity is also examined, and images presented. This technique is only considered to be useful for projective imaging, where it is shown to have an SNR advantage over established methods. Using two specially designed phantoms the accuracy of all these techniques is shown to be within 5%.

Blood flow to the previously active skeletal muscle remains elevated for several hours following an acute bout of aerobic exercise and is dependent on activation of H1 and H2 histamine receptors. Many questions remain unanswered in humans regarding the mechanisms mediating this sustained post-exercise vasodilation and what benefits come of this physiological phenomenon. The studies detailed in this dissertation were designed to examine the upstream mechanisms and explore a potential benefit associated with sustained post-exercise vasodilation. In chapter IV, we examined if oxidative stress is the upstream exercise-related factor mediating sustained post-exercise vasodilation. Intravenously infusing the antioxidant ascorbate blunted sustained post-exercise vasodilation, and this reduction was similar in magnitude to that observed with H1/H2 blockade. However, ascorbate may directly degrade histamine and may also inhibit its formation. Therefore, we conducted a follow-up study to verify the findings in study 1. In this study, we intravenously infused n-acetylcysteine, a potent antioxidant with no known histaminergic interactions. We found that n-acetylcysteine had no effect on sustained post-exercise vasodilation, indicating that exercise-induced oxidative stress is not the exercise related factor mediating sustained post-exercise vasodilation. In chapter V, we attempted to measure interstitial histamine in an effort to demonstrate that exercise induces the local formation of histamine in previously active skeletal muscle. We found that histamine is increased in the interstitial fluid within skeletal muscle during and after exercise. Additionally, we determined that de novo synthesis via histidine decarboxylase contributes to the rise in histamine during and following exercise. We also demonstrated a possible role of mast cells as an additional mechanism augmenting histamine in skeletal muscle. Collectively, these studies demonstrate that histamine is the ligand activating histamine receptors and activation is due to the induction of histidine decarboxylase and mast cell activation. In chapter VI, we attempted to determine if histamine receptor activation contributes to the expression of pro- and anti-angiogenic growth factors during the recovery from exercise. Our preliminary findings indicate that activation of histamine receptors may play a role in the expression of pro-angiogenic growth factors during the recovery from acute aerobic exercise.

Hypothermia has been shown to provide protective benefits to the brain after head trauma. Current treatment methods employ full body hypothermia which can lead to further associated complications, such as a compromised immune system. Alternatively, cooling the brain individually can provide the same benefits whilst minimising the risks associated. Unfortunately, the feasibility of this is still uncertain due to the invasiveness of measuring cerebral temperatures directly and the unavailability of brain temperature maps. Mathematical modelling provides an important alternative avenue for predicting the outcome of hypothermic procedures, such as scalp cooling. However, these tend to rely on Pennes Bioheat Equation which simplifies the blood flow within the system as a single perfusion term. This removes any directional thermal advection which could play an important part in biological heat transfer. In this thesis, an alternative method is developed, tested, and proposed where the full cerebral circulatory system is modelled using vascular channels embedded in a porous tissue simulating the blood vessels and capillaries, respectively. This is dubbed the vascular porous (VaPor) method. This dissertation tests and discusses the feasibility of inducing hypothermia by cooling the scalp using the VaPor model. Initially, the blood vessels were modelled in 3D to fully capture the effects of flow, however, this was deemed computationally inefficient and difficult to manipulate so was subsequently replaced with a system of 1-Dimensional line segments. Temperatures produced from this method conform to expected ranges of values and agree with available data from studies in rat brains. It was observed that core brain temperatures can be impacted by scalp cooling but only with a large number of generated vessels. This is due to the tortuous nature of the vasculature which is not captured by the porous media alone. Various input parameters are also tested to ensure the validity of results from this model. One tested parameter that did not agree with in-vivo results was the measurement of tissue perfusion which appeared to be grossly exaggerated by the VaPor model, although conservation of mass was conserved at each stage. This was investigated further by simulating tracer transport in the cerebral domain in the same manner that in-vivo measurements use. While in-vivo measurements and the predictions by tracer transport produce perfusion values of the same order of magnitude, a full quantitative match cannot be expected because of the differences in the measurement techniques used. Various approximations that can be imposed to resolve this are discussed. The versatility of the VaPor model was explored by simulating a variety of applications relevant to cerebral cooling. The inclusion of counter-current flow within the porous domain showed similar results to trials performed with dense vascular trees. Trials on the scale of a neonatal brain showed that hypothermia could be achieved from scalp cooling alone contrary to previous models. The transient response of scalp cooling was explored as well as the thermal response after simulating an ischemic stroke. All results demonstrated that, due to the inclusion of directional flow, scalp cooling has a larger impact on cerebral temperatures than seen with previous bioheat models.

The Spiral Vortex (SV) ventricular assist device (VAD) was investigated by 2-component laser Doppler anemometry (LDA) while pumping a refractive index-matched blood analogue fluid. The VAD was operated under physiological conditions corresponding to 75% assist (4 litres/minute) or weaning from assist (2 litres/minute). Data were sampled on a 5-mm grid throughout most of the interior of the blood chamber, using two orthogonal LDA configurations from which 3D velocity data were synthesised. Data were subjected to statistical analysis of quasistatic time intervals and approximation by Fourier series. The velocity vector fields were explored statically (via 2D plots) and dynamically (using 3D animations of the reduced data). Reynolds stresses were computed and visualised in 2D. Fluid pathlines were simulated and plotted in 3D. The flow was found to be dominated by an irrotational vortex that accelerated and precessed in phase with the pumping diaphragm. Two unexpected flow structures, a rising, swirling near-wall layer in diastole and a reflection of the outflow vortex upon valve closure, enhanced washing of the walls. The thickness of the boundary layer was estimated to be 2 mm. Fluid velocities were generally lower than those reported in steady-flow studies on the SV VAD, although turbulence was comparable. Under the weaning mode, the coherence of the main vortex was degraded and flow recirculation was observed distal to the inflow port; this operating mode must be regarded as an indication for anticoagulation. In both pumping modes, turbulence was elevated in association with asymmetric buckling of the pneumatically driven diaphragm. Suboptimal orientation of the tilting-disc inlet valve gave rise to augmented turbulence production and skewing of the main vortex; similar results were obtained for an axisymmetric polymer (Jellyfish) valve, despite its advantageous haemodynamics. Flow stagnation was apparent where the inflow stream impinged on the wall, opposite the inflow port. The overall design of the SV VAD appears to almost ideal, in the context of current technology. However, elimination of recirculation/stagnation zones, especially in the weaning mode, remains a priority for the ultimate optimisation of haemocompatibility. Pulsatile VADs will probably never be entirely free of flow recirculation or stagnation, and published claims to the contrary probably reflect study limitations.

Thesis (M. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Exercise and/or heat-induced dehydration is associated with decreases in plasma volume (hypovolemia) and increases in plasma osmolality (hyperosmolality), which are thought to stimulate peripheral baroreceptors and central osmoreceptors respectively. Independently, plasma hyperosmolality and baroreceptor unloading have been shown to attenuate sweating and cutaneous vasodilation during heat stress, and therefore, negatively impact body temperature regulation. However, to date little is known regarding the combined influence of plasma hyperosmolality and baroreceptor unloading on thermoefferent activity. Therefore, we evaluated the separate and combined effects of baroreceptor unloading (via lower body negative pressure, LBNP) and plasma hyperosmolality (via infusion of 3% NaCl saline) on heat loss responses of sweating and cutaneous vascular conductance (CVC) during progressive whole-body heating. We show that the combined nonthermal influences of plasma hyperosmolality and baroreceptor unloading additively delay the onset threshold for CVC, relative to their independent effects. In contrast, baroreceptor unloading has no influence on the sweating response regardless of osmotic state. These divergent roles of plasma hyperosmolality and the baroreflex on heat loss responses might serve to enhance blood pressure and body core temperature regulation during dehydration and heat stress.

Exercise and/or heat-induced dehydration is associated with decreases in plasma volume (hypovolemia) and increases in plasma osmolality (hyperosmolality), which are thought to stimulate peripheral baroreceptors and central osmoreceptors respectively. Independently, plasma hyperosmolality and baroreceptor unloading have been shown to attenuate sweating and cutaneous vasodilation during heat stress, and therefore, negatively impact body temperature regulation. However, to date little is known regarding the combined influence of plasma hyperosmolality and baroreceptor unloading on thermoefferent activity. Therefore, we evaluated the separate and combined effects of baroreceptor unloading (via lower body negative pressure, LBNP) and plasma hyperosmolality (via infusion of 3% NaCl saline) on heat loss responses of sweating and cutaneous vascular conductance (CVC) during progressive whole-body heating. We show that the combined nonthermal influences of plasma hyperosmolality and baroreceptor unloading additively delay the onset threshold for CVC, relative to their independent effects. In contrast, baroreceptor unloading has no influence on the sweating response regardless of osmotic state. These divergent roles of plasma hyperosmolality and the baroreflex on heat loss responses might serve to enhance blood pressure and body core temperature regulation during dehydration and heat stress.

Atherosclerotic plaques with high probability of rupture show the presence of a hot spot due to the accumulation of inflammatory cells. This study utilizes two and three dimensional (2-D and 3-D) arterial geometries containing an atherosclerotic plaque experiencing different levels of inflammation and uses models of heat transfer analysis to determine the temperature distribution in the plaque region. The 2-D studies consider three different vessel geometries: a stenotic straight artery, a bending artery and an arterial bifurcation which model a human aorta, a coronary artery and a carotid bifurcation, respectively. The 3-D model considers a stenotic straight artery using realistic and simplified geometries. Three different blood flow cases are considered: steady-state, transient state and blood flow reduction. In the 3-D model, thermal stress produced by local inflammation is estimated to determine the effect of inflammation over plaque stability. For fluid flow and heat transfer analysis, Navier-Stokes equations and energy equation are solved; for structural analysis, the governing equations are expressed in terms of equilibrium equation, constitutive equation, and compatibility condition, which are are solved using the multi-physics software COMSOL 3.3 (COMSOL, Inc.). Our results indicate that the best location to measure plaque temperature in the presence of blood flow is recommended between the middle and the far edge of the plaque. The blood flow reduction leads to a non-uniform temperature increase ranged from 0.1 to 0.25 oC in the plaque/lumen interface. In 3-D realistic model, the multiple measuring points must be considered to decrease the potential error in temperature measurement even within 1 or 2 mm at centerline region of plaque. The most highly thermal stressed regions with the value of 1.45 Pa are observed at the corners of lipid core and the plaque/lumen interface. The mathematical model developed provides a tool to analyze the factors affecting heat transfer at the plaque surface. The results may contribute to the understanding of the relationship between plaque temperature and the likelihood of rupture, and also provide a tool to better understand arterial wall temperature measurements obtained with novel catheters.

名古屋大学博士学位論文 学位の種類 : 博士(医学)(論文) 学位授与年月日:平成7年12月20日 北川喜己氏の博士論文として提出された

Hypoxia (decreased tissue oxygen levels) has long been considered as a possible mechanism of alcohol-induced developmental deficits, yet research has not conclusively disproved this hypothesis, nor has it provided substantial evidence for a mechanism of developmental alcohol insults involving hypoxia. Previous research has shown that moderate acute doses of alcohol does not induce hypoxemia (decreased arterial oxygen levels), yet these same studies have shown that this same alcohol exposure does transiently decrease cerebral blood flow (CBF). This is significant because although developmental alcohol exposure did not result in hypoxemia, the decreases in CBF seen in these previous studies may induce hypoxia within the brain. Unfortunately, these experiments were only performed after acute doses of alcohol, so it is unknown if a more chronic or repeated alcohol exposure paradigm would have similar effects. The present study examined blood flow in the sheep fetus after repeated alcohol exposure in a bingelike paradigm throughout the third trimester. Additionally, this study examined the fetal neurovascular response to a subsequent infusion of alcohol after the repeated alcohol exposure. This latter experiment was designed to examine the hypothesis that alcohol exposure throughout the third trimester affects the normal responsiveness of the neurovasculature to alcohol (compared to previous research demonstrating acute alcohol-induced decreases in CBF). The results from the present experiments indicate that although few regions were significant, the majority of the regions (especially the brain regions) exhibited a trend for increases in blood flows after alcohol exposure. This phenomenon was especially prominent in the group receiving the lower dose of alcohol. Additionally, the data from this study demonstrated that after repeated alcohol exposures the near-term sheep fetus did not respond to a subsequent dose of alcohol in a similar manner seen in previous experiments when the acute alcohol exposure was administered in alcohol naïve animals. After the final alcohol exposure the subjects in this study had either no effect in terms of blood flow or an increase in CBF. This is opposite to previous observations which demonstrated reduced blood flow in numerous brain regions. The present experiments suggest that alcohol does not induce fetal hypoxia, but does negatively affect the normal neurovascular response to alcohol. This latter phenomenon could have negative consequences on future development of the brain.