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This work represents the next step in the ongoing development of a system to noninvasively estimate blood perfusion using thermal methods. A combination thermocouple/thermopile sensor records heat flux and temperature measurements on the tissue of interest (in this case skin) for a given period of time. These data, in combination with other experimental parameters, are read into a computer program that compares them to a biothermal finite difference model of the system. The program uses an iterative process incorporating Gauss Minimization to adjust parameters in the biothermal model until the predicted system behavior satisfactorily approximates the real world data. The result is an estimation of blood perfusion in the tissue being measured, as well as an estimate of the thermal contact resistance between the probe and tissue. The system is tested on human forearms, canine legs during laparoscopic spay surgery, and on a canine medial saphenous fasciocutaneous free tissue flap model. Experimental measurements, especially those performed on the tissue flap model, show distinct correlation between blood perfusion and bioprobe output. This research demonstrates the accuracy of the biothermal model and the parameter estimation technique, as well as the usability of the system in a clinical setting. / Master of Science

PURPOSE: This study examined the effects of creatine (Cr) supplementation and blood flow restriction (BFR) on muscle strength, neuromuscular function, body composition, and endothelial health in women across 8 weeks of training. METHODS: Recreationally active women (n= 59) were randomized into one of five groups: BFR-Pl (BFR exercise and placebo), BFR-Cr (BFR exercise and creatine supplementation), Pl (low-load exercise without BFR and placebo), Cr (low-load exercise without BFR and creatine supplementation), or Control (no exercise, BFR, or supplementation). Assessments of isometric strength, concentric strength, neuromuscular responses, muscle size, body composition, and endothelial function were evaluated at baseline, post-loading (after 5 days of supplementation), 4 weeks, and 8 weeks. RESULTS: All groups experience similar increases in measures of isometric strength (6.5%), muscle thickness (2.9%), cross sectional area (4.1%), body mass (2.8%), and total body water (1.2%). There were no significant changes in neuromuscular parameters or endothelial function for any of the groups across the 8-week intervention. The BFR and Cr groups (10.6 – 15.7%), however, experienced larger increases in concentric strength compared to placebo and control groups (6%). CONCLUSION: The results of the present study indicated that BFR and creatine alone are potent stimulators for muscle strength and muscle growth but may not have additive benefits. Further, the supplementation of creatine throughout this 8-week training program did effect body mass or total body water. Overall, resistance exercise, BFR and Cr can be used independently or together to induce positive muscular adaptations among women.

Master of Science / Department of Kinesiology / Thomas Barstow / Previously in our laboratory, capillary blood flow (QCAP) kinetics were found to be significantly slower than femoral artery (QFA) kinetics following the onset of knee extension exercise. If the increase in QCAP does not follow a similar time course to QFA, blood must be flowing into the leg but not to the working muscle. One possible explanation for this discrepancy is that blood flow also increases to the nonworking lower leg muscles. Purpose: To determine if cuffing below the knee alters the kinetics of QFA and QCAP during knee extension exercise, and provide insight into the potential mechanisms controlling the rapid increase in QFA. Methods: Subjects performed a ramp max test to determine the work rate at which gas exchange threshold (GET) occurred. At least four constant work rate trials in each condition were conducted at work rates eliciting ~80% GET. Trials were performed with and without below knee occlusion. Pulmonary gas exchange, near-infrared spectroscopy, QFA and mean arterial pressure (MAP) measurements were taken. Muscle oxygen uptake (VO2m) and deoxy[hemoglobin + myoglobin] were used to estimate QCAP. Conductance (C) was calculated (QFA/MAP) and the percent change from baseline at 60s into exercise was calculated to indicate a time course of change. Results: There was no significant difference between the uncuffed and cuffed conditions (P>0.05). The mean response times (MRT) of QFA were 18.7 ± 14.2s (uncuffed) and 24.6 ± 14.9s (cuffed). QCAP MRTs were 51.8 ± 23.4s (uncuffed) and 56.7 ± 23.2s (cuffed), which were not significantly different from the time constants (τ) of VO2m (39.7 ± 23.2s (uncuffed) and 46.3 ± 24.1s (cuffed)). However, the MRT of QFA was significantly faster (P<0.05) than the MRT of QCAP and τVO2m. τVO2m and MRT QCAP were significantly correlated. The QFA and C percent increase from baseline at 60s were significantly different from MAP but not from each other. Conclusion: Cuffing below the knee did not significantly change the kinetics of QFA, QCAP or VO2m. Estimated QCAP kinetics tracked VO2m following exercise onset, while changes in QFA appeared to be primarily driven by an increase in C, not an increase in MAP.

Low load resistance training (LLRT) with blood flow restriction (BFR) is a novel form of exercise that has been demonstrated to increase muscle mass and strength. Combined with the fact that as individuals age they lose both of these parameters, LLRT with BFR has been put forward as a method to help reverse/prevent the associated sarcopenia of ageing. This research investigated the effect the effect of LLRT with BFR on muscle strength firstly in younger people and then an older population group following 4 weeks of training. Muscle function measurements of young and old people included dynamic strength, identified as one repetition maximum (1 RM), isometric strength and isokinetic torque at a range of velocities (0.52 2.09 rad.s-1). Vascular adaptations were also measured using venous occlusion plethysmography to assess rest blood flow (Rbf) and post occlusive reactive hyperemia (PObf). The mechanisms behind any adaptations were measured following acute responses of plasma hormones and growth factors (cortisol, growth hormone (GH), insulin like growth factor 1 (IGF-1), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF)) as well as local skeletal muscle gene expression (IGF-1Ea and MGF mRNA) to LLRT with BFR. LLRT with BFR increased (P < 0.05) all measurements of muscle strength by 13 30% in both young and older people. PObf was also increased (P < 0.05) following 4 weeks of LLRT with BFR in both population groups. Acute responses to LLRT with BFR identified an increase (P < 0.05) in GH and VEGF in older people. These are similar response to those seen in the young. Finally local gene expression of MGF mRNA was elevated (P < 0.05) 24 hours post LLRT with BFR in both young and older people. Any changes in muscle and blood flow adaptations may be as a result of increased hormones and growth factors at a circulation and local level. Key words: Blood flow restriction, blood flow, muscle strength, growth hormone, IGF-1

Many cardiovascular diseases are partly due to heart muscle malfunctions. The main dynamic function in the heart is metabolism via mitochondrial respiration. And the most direct measure of oxidative tissue metabolism is the conversion rate of oxygen to water. Finding the oxygen consumption rate in the heart vessel will help us prevent the heart diseases. In the experiment, 15O-labeled RBCs (Red Blood Cells) and indocyanine green dye were injected into the isolated blood-perfused rabbit heart. The dye curves defined the inflow for the dye have the same shape as the inflow curves for the 15O oxygen. The inflow and outflow dilution curves for 15O were obtained with use of PET (Positron Emission Tomography) technology. After appropriate correction for baseline and radioactive decay, the data were transferred to a UNIX workstation for model analysis. A linear, three-region (capillary space, interstitial fluid space, and parenchymal cell space), and axially distributed model is introduced to simulate the oxygen consumption process and determine the oxygen conversion rate. Parameters of concentration are oxygen and water corresponding to capillary space, interstitial fluid space, and parenchymal cell space. The diffusion coefficients are largely independent of molecular motion. The blood flow happens only in capillary part. Other parameters are determined by experimental data. Using the input data, consumption rate is determined through a process minimizing the difference between the experimental and numerical output. Effects of key parameters on oxygen concentration and consumption rate are investigated.

The flow of blood in the human body is a very important component in un-derstanding a number of different ailments such as atherosclerosis and a falseaneurysm. In this thesis, we have utilized Poiseuille’s solution to Navier-Stokesequations with a Newtonian, incompressible fluid flowing laminar with zero ac-celeration in a pipe with non-flexible walls in order to study blood flow in anarterial tree. In order to study and simulate a larger arterial tree we have uti-lized a primitive building block, a bifurcation with one inlet and two outlets,joined together forming a tree. By prescribing an inlet flow and the pressureat every outlet at the bottom of the tree we have shown that we may solvethe system by fixed-point iteration, the Matlab functionfsolve, and Newton’smethod. This way of using primitive building blocks offers a flexible way to doanalysis as it makes it possible to easily change the shape of the tree as well asadding new building blocks such as a block that represents arteriosclerosis.

Background. Extensive studies have been conducted to simulate blood flow in the human vasculature using nonlinear equations of pulsatile flow in collapsible tube plus a network of vessels to represent the whole vasculature and the cerebral circulation. For non-linear models numerical solutions are obtained for the fluid flow equations. Methods. Equations of fluid motion in collapsible tubes were developed in the presence of gravitational force (Gforce). The Lax-Wendroff and MacCormack methods were used to solve the governing equations and compared both in terms of accuracy, convergence, and computer processing (CPU) time. A modified vasculature of the whole body and the cerebral circulation was developed to obtain a realistic simulation of blood flow under different conditions. The whole body vasculature was used to validate the simulation in terms of input impedance and wave transmission. The cerebral vasculature was used to simulate conditions such as presence of G-force, blockage of Internal Carotid Artery (ICA), and the effects on cerebral blood flow of changes in mean and pulse pressure. Results. The simulation results for zero G-force were in very good agreement with published experimental data as was the simulation of cerebral blood flow. Both numerical methods for solutions of governing equations gave similar results for blood flow simulations but differed in calculation performance and stability depending on levels of G-force. Simulation results for uniform and sinusoidal G-force are also in good agreement with published experimental results, Blood flow was simulated in the presence of a single (left) carotid artery obstruction with varying morphological structures of the Circle of Willis (CoW). This simulation showed significant differences in contralateral blood flow in the presence or absence of communicating arteries in the CoW. It also was able to simulate the decreases in blood flow in the cerebral circulation compartment corresponding to the visual cortex in the presence of G-force. This is consistent with the known loss of vision under increased acceleration. Conclusions. This study has shown that under conditions of gravitational forces physiological changes in blood flow in the systemic and cerebral vasculature can be simulated realistically by solving the one-dimentional fluid flow equations and non-linear vascular properties numerically. The simulation was able to predict changes in blood flow with different configurations and properties of the vascular network.

Introduction: Oxygen delivery, or utilization, is a function of retinal blood flow and blood oxygen saturation. The retinal pigment epithelium (RPE), in particular, has been shown to have the highest levels of metabolic activity within the human body. Oxygen delivery is therefore of extreme importance to the maintenance of the health and integrity of the retina. Animal models presuppose that the oxygen tension in the retina is highest in the innermost layers at the level of the choriocapillaris, less in the photoreceptors and further decreases throughout the outer retinal structures. The choroid provides by far the largest component of the oxygen for consumption by the photoreceptors. A lack of oxygen stores in the inner retina therefore makes a constant supply crucial for its normal functioning. Blood flow dysfunction and subsequent hypoxia are both a feature in the pathogenesis of several major ocular diseases such as retinopathy of prematurity (ROP), age-related macular degeneration (ARMD), diabetic retinopathy (DR) and glaucoma. The development of methods to measure retinal blood flow and blood oxygen saturation is crucial to improve understanding of the patho-physiology of major ocular diseases. Purpose: The aims of this work were, firstly, to determine the least variable (range ± standard deviation) wavelength combination (610/548, 600/569 and 605/586) and subsequent ODR with the prototype HRC device. Secondly, using the ODR with the lowest measurement variability, we sought to quantify retinal blood SO2 in arterioles and venules and investigate the relationship between retinal blood SO2 and total retinal blood flow (TRBF) in response to stepwise changes in PETO2 in healthy participants. Retinal blood SO2 and TRBF were assessed using the IRIS HRC (Photon etc. Inc. Montreal, Canada) and the RTvue Doppler Fourier Domain OCT (Optovue Inc, Freemont, CA) instruments, respectively. Methods: Ten healthy participants between the ages of 23 and 37, with an average age of 28.3 years were evaluated in two descriptive cross-sectional studies. Two gas provocation protocols; hyperoxia (end-tidal oxygen; PETO2 of 100, 200, 300, 400mmHg) and hypoxia (PETO2 of 100, 80, 60, 50mmHg) were administered in a fixed sequential order. In each phase of gas provocation (via modulation of PETO2), retinal blood SO2 and TRBF measurements were acquired with the HRC and Doppler FD-OCT. The precise and repeated control of the partial end tidal pressures of oxygen (PETO2) and carbon dioxide (PETCO2) over the pre-determined phase duration, irrespective of the individuals’ respiratory rate, was made possible with the RespirAct (Thornhill Research Inc., Toronto, Canada); a sequential re-breathing gas delivery Results: In arterioles, the group range (±SD) of ODR values for baseline measurements (PETO2 of 100mmHg) was 0.169±0.061 for the 605/586 wavelength combination, 0.371±0.099 for the 600/569 wavelength combination and 0.340±0.104 for the 610/548 wavelength combination. In venules, the group range (±SD) of ODR values was 0.600±0.198 for the 605/586 wavelength combination, 0.569±0.169 for the 600/569 wavelength combination and 0.819±0.274 for the 610/548 wavelength combination. With the 605/586 combination at baseline 1 and 2 in arterioles, the group range (±SD) of ODR values was 0.607 ± 0.224 and 0.619 ± 0.158, respectively (p = 0.370), while in venules the group range (±SD) of ODR at baseline 1 and 2 was 0.289±0.750 and 0.284 ± 0.729, respectively (p = 0.714). For the 600/569 combination at baseline 1 and 2 in arterioles, the group range (±SD) of ODR values was 0.747±0.350 and 0.761±0.391, respectively (p = 0.424) while in venules the group range (±SD) of ODR at baseline 1 and 2 was 0.329±0.675 and 0.366±0.659, respectively (p = 0.372). For the 610/548 combination at baseline 1 and 2 in arterioles, the group range (±SD) of ODR values was 0.604±0.263 and 0.685±0.450, respectively (p = 0.056) while in venules, the group range (±SD) of ODR at baseline 1 and 2 was 0.292±0.746 and 0.285±1.009, respectively (p = 0.131). There was no statistical difference found between baseline ODR values (baseline 1 and 2) across all three wavelength combinations in both arterioles and venules. The mean retinal blood SO2 value at baseline in arterioles for 4 participants was 95.19% ± 31.04% and venules was 53.89% ± 17.24% (p = 0.115). There was a negative linear relationship between group retinal blood SO2 and TRBF values in the 10 participants studied, although the results of any of the 10 individuals did not show evidence of such a relationship using the described methodology. The Pearson’s correlation coefficient (r) between TRBF and SaO2 was r = -0.354 and p = 0.001 and between TRBF and SvO2 was r = - 0.295, p = 0.008 Conclusion: Of the three wavelength combinations investigated (605/586, 600/569 and 610/548), the 605/586 combination was shown to have the overall least variability. It would be unwise at this stage to adopt this wavelength combination for clinical usage, however, since it is presupposed that the 605/586 combination is also the most reliable combination to detect change in retinal blood SO2 i.e. lower variability of the 605/586 combination may be irrelevant if this combination proves to be insensitive to change in retinal blood SO2. The absolute mean ± SD retinal blood SO2 in the arterioles (SaO2) was 95.19% ± 31.04% and in the venules (SvO2) was 53.89% ± 17.24%. These values fell within the range expected and described in the literature. The magnitude of the difference between the SaO2 and SvO2 was also consistent with the literature. These findings were all appropriate for a low flow, high oxygen exchange vascular network typical of the inner retinal vascular system. Using group rather than individual data, TRBF was found in this study to relate inversely with SaO2 (r = -0.354 and p = 0.001) and SvO2 (r = – 0.295 and p=0.008), respectively. This relationship between TRBF and SaO2 and SvO2, was as expected based upon data derived primarily from animal models. This study is ground-breaking and unique, in that, it is the first study to concomitantly measure both retinal blood SO2 and TRBF in human participants. Individual data showed extensive variability and noise, thus limiting the strength of the association between TRBF and SaO2 and SvO2..