The deposition of ultrasonic energy in tissue can cause tissue damage due to local heating. For pressures above a critical threshold, cavitation will occur in tissue and bubbles will be created. These oscillating bubbles can induce a much larger thermal energy deposition in the local region. Traditionally, clinicians and researchers have not exploited this bubble-enhanced heating since cavitation behavior is erratic and very difficult to control. The present work is an attempt to control and utilize this bubble-enhanced heating. First, by applying appropriate bubble dynamic models, limits on the asymptotic bubble size distribution are obtained for different driving pressures at 1 MHz. The size distributions are bounded by two thresholds: the bubble shape instability threshold and the rectified diffusion threshold. The growth rate of bubbles in this region is also given, and the resulting time evolution of the heating in a given insonation scenario is modeled. In addition, some experimental results have been obtained to investigate the bubble-enhanced heating in an agar and graphite based tissue- mimicking material. Heating as a function of dissolved gas concentrations in the tissue phantom is investigated. Bubble-based contrast agents are introduced to investigate the effect on the bubble-enhanced heating, and to control the initial bubble size distribution. The mechanisms of cavitation-related bubble heating are investigated, and a heating model is established using our understanding of the bubble dynamics. By fitting appropriate bubble densities in the ultrasound field, the peak temperature changes are simulated. The results for required bubble density are given. Finally, a simple bubbly liquid model is presented to estimate the shielding effects which may be important even for low void fraction during high intensity focused ultrasound (HIFU) treatment.

A complete understanding of high-intensity focused ultrasound-induced temperature changes in tissue requires insight into all potential mechanisms for heat deposition. Applications of therapeutic ultrasound often utilize acoustic pressures capable of producing cavitation activity. Recognizing the ability of bubbles to transfer acoustic energy into heat generation, a study of the role bubbles play in tissue hyperthermia becomes necessary. These bubbles are typically less than 50μm. This dissertation examines the contribution of bubbles and their motion to an enhanced heating effect observed in a tissue-mimicking phantom. A series of experiments established a relationship between bubble activity and an enhanced temperature rise in the phantom by simultaneously measuring both the temperature change and acoustic emissions from bubbles. It was found that a strong correlation exists between the onset of the enhanced heating effect and observable cavitation activity. In addition, the likelihood of observing the enhanced heating effect was largely unaffected by the insonation duration for all but the shortest of insonation times, 0.1 seconds. Numerical simulations were used investigate the relative importance of two candidate mechanisms for heat deposition from bubbles as a means to quantify the number of bubbles required to produce the enhanced temperature rise. The energy deposition from viscous dissipation and the absorption of radiated sound from bubbles were considered as a function of the bubble size and the viscosity of the surrounding medium. Although both mechanisms were capable of producing the level of energy required for the enhanced heating effect, it was found that inertial cavitation, associated with high acoustic radiation and low viscous dissipation, coincided with the the nature of the cavitation best detected by the experimental system. The number of bubbles required to account for the enhanced heating effect was determined through the numerical study to be on the order of 150 or less.

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Athletes use a wide range of interventions to promote recovery from strenuous exercise, but few data are available regarding the efficacy of such practices. OBJECTIVE: To examine the effectiveness of commonly used interventions [Rest, light exercise (AR), contrast therapy (CT) and cryotherapy (CR)] during recovery between bouts of intense exercise. We tested the hypothesis that hydrotherapy interventions (CT and CR) would induce favorable physiological and/or psychological alterations such that performance would be improved versus AR and Rest. METHODS: In Study I, 12 active men (25-35 yrs; VO2peak = 46±3 ml·kg-1·min-1; mean±SD) performed 5 consecutive days of HI exercise (4-6 bouts x 30 sec 'all out' Wingate Tests, with 4-min recovery, each day). After each training session, subjects either rested for 20 min (CON, n=6) or completed a CT protocol (n=6) that consisted of alternating cold (10°C) and hot (40°C) tubs using a 4x2:3 min ratio. Performance measures [Peak (Wmax) and mean (Wmean) power, VO2peak, and a 250 kJ Time Trial (TT)] were assessed before and after the HIT. In Study II, 9 active men (29±6 yr, VO2peak = 44±8 ml·kg-1·min-1) performed 3 exercise trials separated by 1 wk. Each trial consisted of 3 x 50 KJ time trials(~100-120%VO2peak) with a different 20-min recovery period [CON, AR (cycling@ SOW) or CR (cold tub@ 10°C)] between rides each week. Venous blood samples were obtained after each recovery period, and analyzed for lactate, interleukin-6, neutrophils, and lymphocytes. Questionnaires designed to assess exercise preparedness were also completed daily in both studies. RESULTS: In Study I, Wmax and TT performance improved after 5 d of HI exercise (time effect, P<0.05), but there were no differences between groups (Wmax-CT: Post: 1310±45 vs Pre: 1215±86; CON: Post: 1343±54 vs Pre: 1220±74 W: TT-CT: Post: 15.8±0.6 vs Pre: 16.7±0.7; Rest: Post: 18.1±1.0 vs Pre: 18.8±1.2 min, means±SEM). In Study II, TT performance averaged 118±10 sec for bout 1 and was 8% and 14% slower during bouts 2 (128±11 sec) and 3 (134±11 sec), respectively, with no difference between treatments (Time effect, P≤0.05). Blood lactate was lower after AR compared to CR and Rest, and neutrophils and lymphocytes were higher and lower respectively (P≤0.05), after CR (8.7±1.3 and 1.4±0.2 x 109cells/L) versus AR (7.1±1.0 and 1.6±0.1) and Rest (6.7±0.7 and 1.6±0.1). With respect to the psychological measurements, the CT and CR groups in both studies reported feeling more revitalized after each treatment session and greater preparedness for subsequent exercise (Treatment effect, P≤.05). CONCLUSIONS: Exercise performance during repeated bouts of intense cycling was not influenced by the type of recovery intervention employed, either during a single session or over the course of a 5 d training session. CR caused greater perturbations in blood immune markers and most notably, hydrotherapy interventions created the perception that subjects were better prepared for subsequent exercise. / Thesis / Master of Science (MS)

This thesis is missing page 63 from all copies. -Digitization Centre / Manipulating carbohydrate (CHO) availability has been shown to alter acute exercise-induced changes in metabolic gene transcription and training-induced changes in oxidative capacity. The present study examined the effect of CHO availability on signalling pathways linked to mitochondrial biogenesis in response to high-intensity interval exercise (HIE). We hypothesized that reduced CHO availability would augment phosphorylation of AMP-activated protein kinase (AMPK), calcium/calmodulin-dependent kinase II (CaMKII), and p38 mitogen-activated protein kinase (p38) in response to HIE. Ten active men performed two experimental trials in random order, separated by 2:1 wk. During each trial, subjects performed two HIE sessions separated by 3 h (AM and PM sessions). Exercise sessions consisted of 5 x 4 min cycling bouts at a workload that elicited approximately 90% V02peak, with 2 min rest periods. Between sessions, subjects ingested -1.2 g CHO/kg b.w./h (HI-HI) or a taste-matched, non-energetic placebo (HI-LO). Muscle biopsies and blood samples were obtained before (Pre) and after (Post) the AM and PM HIE sessions. AMPK, CaMKII, and p38 MAPK phosphorylation increased from AM Pre to AM Post (p<0.01). During the PM exercise session, p38 phosphorylation increased in the HI-LO condition (-4.5-fold, p<0.001), whereas the HI-HI condition remained unchanged. PM HIE significantly increased CaMKII phosphorylation independent of condition, while no exercise or condition-mediated AMPK effects were observed. In summary, restricting CHO availability following an acute session of HIE augmented the exercise-induced increase in p38 phosphorylation during a subsequent HIE session. It remains to be determined whether chronic changes in p38 MAPK signalling are mechanistically linked to altered skeletal muscle remodelling observed after CHO-restricted exercise training. / Thesis / Master of Science (MS)

Master of Science / Department of Kinesiology / Craig A. Harms / High-intensity interval training (HIT) has been utilized as a time-efficient strategy to induce numerous physiological adaptations and improve performance usually associated with “traditional” endurance training (ET). It is not known however, if HIT might lead to improvements in pulmonary function. Therefore we hypothesized that HIT would increase respiratory muscle strength and expiratory flow rates. Fifteen healthy subjects were randomly assigned to an ET group (n = 7) and a HIT group (n = 8). All subjects performed an incremental test to exhaustion (VO2 max) on a cycle ergometer prior to and after training. Standard pulmonary function tests, maximum inspiratory pressure (PImax), maximum expiratory pressure (PEmax), and maximal flow volume loops, were performed pre training and after each week of training. HIT subjects performed a four week training program on a cycle ergometer at 90% of their VO2 max final workload while the ET subjects performed exercise at 60-70% of their VO2 max final workload. All subjects trained three days/ week. The HIT group performed five one-minute bouts with three minute recovery periods and the ET group cycled for 45 minutes continuously at a constant workload. A five-mile time trial was performed prior to training, after two weeks of training, and after four weeks of training. Both groups showed similar (p<0.05) increases in VO2 max (~8-10%) and improvements in time trials following training (HIT 6.5 ± 1.3%, ET 4.4 ± 1.8%) with no difference (p>0.05) between groups. Both groups increased (p<0.05) PImax post training (ET ~25%, HIT ~43%) with values significantly higher for HIT than ET. There was no change (p>0.05) in expiratory flow rates with training in either group. These data suggest that whole body exercise training is effective in increasing inspiratory muscle strength with HIT leading to greater improvements than ET. Also, HIT offers a time-efficient alternative to ET in improving aerobic capacity and performance.

Laser induced shock experiments were performed to study the dynamics of various solid state material processes, including shock-induced melt, fast rate fracture, and elastic to plastic response. Fast rate fracture and dynamic yielding are greatly influenced by microstructural features such as grain boundaries, impurity particles and alloying atoms. Fast fracture experiments using lasers are aimed at studying how material microstructure affects the tensile fracture characteristics at strain rates above 106 s-1. We used the Z-Beamlet Laser at Sandia National Laboratories to drive shocks via ablation and we measured the maximum tensile stress of aluminum targets with various microstructures. Using a velocity interferometer and sample recovery, we are able to measure the maximum tensile stress and determine the source of fracture initiation in these targets. We have explored the role that grain size, impurity particles and alloying in aluminum play in dynamic yielding and spall fracture at tensile strain rates of ~3x106 s-1. Preliminary results and analysis indicated that material grain size plays a vital role in the fracture morphology and spall strength results. In a study with single crystal aluminum specimens, velocity measurements and fracture analysis revealed that a smaller amplitude tensile stress was initiated by impurity particles; however, these particles served no purpose in dynamic yielding. An aluminum-magnesium alloy with various grain sizes presented the lowest spall strength, but the greatest dynamic yield strength. Fracture mode in this alloy was initiated by both grain boundaries and impurity particles. With respect to dynamic yielding, alloying elements such as magnesium serve to decrease the onset of plastic response. The fracture stress and yield stress showed no evidence of grain size dependence. Hydrodynamic simulations with material strength models are used to compare with our experiments. In order to study the strain rate dependence of spall in aluminum we used a shorter pulsed laser and thinner targets. From these experiments we do not observe an increase in spall strength for aluminum up to strain rates of ~2x107 s-1. / text

Given the great promise of High Intensity Focused Ultrasound (HIFU) as a therapeutic modality, the aim of the present study is to develop and optimise a technique that uses externally applied focused ultrasound energy and remote, ultrasound-based treatment monitoring to destroy subcutaneous fat safely, effectively and non-invasively. Based on initial cavitation and temperature measurements performed ex vivo in excised porcine fat at four different frequencies (0.5, 1.1, 1.6 & 3.4MHz) over a range of pressure amplitudes and exposure durations, it was concluded that 0.5MHz is the optimal frequency for this application since it is capable of instigating inertial cavitation at relatively modest pressures while enhancing focal heat deposition. Histological assessment of tissue treated above the cavitation threshold at 0.5MHz both ex vivo and in vivo demonstrated damage to adipocytes and connective tissue. Furthermore, a good correlation was identified between the energy of broadband emissions detected by the passive cavitation detector (PCD) and the focal temperature rise at 0.5MHz during ex vivo experimentation, which could be exploited as a tool for non-invasive monitoring of successful treatment delivery. In addition, localisation of cavitation activity by means of passive cavitation detection was achieved and shown to provide a strong indicator of the location of induced histological damage. Based on the specific requirements identified during initial experimentation, an application-specific HIFU transducer, cavitation detector and real-time treatment monitoring software was developed and tested ex vivo. This treatment system was found capable of producing extensive damage to adipocytes and collagen confined to the subcutaneous fat layer at the desired treatment depth, which coincided with the location of cavitation activity as displayed by the real-time treatment monitoring software.

Master of Science / Department of Kinesiology / Craig A. Harms / Subjects with prehypertension are at risk for developing hypertension (HTN). Hypertension is associated with low-grade systemic inflammation (LGSI). Aerobic exercise training (ET) is a proven means to reduce both blood pressure and LGSI in healthy and diseased subjects. Recently, high intensity interval training (HIIT) has been show to elicit similar cardiovascular and metabolic adaptations as ET in healthy and at-risk populations in a more time efficient manner. Therefore, we hypothesized that HIIT would elicit greater reductions in blood pressure and LGSI than ET. Twelve pre-hypertensive subjects (systolic blood pressure 127.0 ± 8.5 mmHg; diastolic blood pressure 86.2 ± 4.1 mmHg) were randomly assigned to an ET group (n=5) and a HIIT group (n=7). All subjects performed an incremental test to exhaustion (VO2max) on a cycle ergometer prior to, after 4 weeks, and after 8 weeks of training. Resting heart rate and blood pressure were measured prior to and three times a week during training. LGSI was measured via high-sensitivity C-reactive protein (hs-CRP) prior to, after 4 weeks and after 8 weeks of training. ET subjects performed an eight week exercise training program at 40% VO2 reserve determined from the VO2max test, while HIIT subjects performed exercise at 60% peak power determined from the VO2max test. ET group trained four days/week while HIIT trained three days/week. ET exercised for 30 minutes continuously at a constant workload and cadence of 60 rpm while HIIT performed a protocol on a 1:1 work-to-rest ratio at a constant workload and cadence of 100 rpm. Both groups showed similar (p<0.05) decreases in mean arterial (ET = -7.3%, HIIT = -4.5%), systolic (ET = -6.6%, HIIT = -8.8%), and diastolic (ET= -9.7, HIIT= -8.2%) blood pressure. HIIT decreased in LGSI (-33.7%) while ET did not change LGSI (p>0.05). VO2max increased ~25% with both HIIT and ET with no differences (p>0.05) between groups. These data suggest both HIIT and ET similarly decreased resting blood pressure and increased VO2max while HIIT was effective in decreasing LGSI in subjects who were pre-hypertensive.

Malignant or benign tumors may be ablated with high‐intensity focused ultrasound (HIFU). This technique, known as focused ultrasound surgery (FUS), has been actively investigated for decades, but slow to be implemented and difficult to control due to lack of real‐time feedback during ablation. Two methods of imaging and monitoring HIFU lesions during formation were implemented simultaneously, in order to investigate the efficacy of each and to increase confidence in the detection of the lesion. The first, Acousto‐Optic Imaging (AOI) detects the increasing optical absorption and scattering in the lesion. The intensity of a diffuse optical field in illuminated tissue is mapped at the spatial resolution of an ultrasound focal spot, using the acousto‐optic effect. The second, Harmonic Motion Imaging (HMI), detects the changing stiffness in the lesion. The HIFU beam is modulated to force oscillatory motion in the tissue, and the amplitude of this motion, measured by ultrasound pulse‐echo techniques, is influenced by the stiffness. Experiments were performed on store‐bought chicken breast and freshly slaughtered bovine liver. The AOI results correlated with the onset and relative size of forming lesions much better than prior knowledge of the HIFU power and duration. For HMI, a significant artifact was discovered due to acoustic nonlinearity. The artifact was mitigated by adjusting the phase of the HIFU and imaging pulses. A more detailed model of the HMI process than previously published was made using finite element analysis. The model showed that the amplitude of harmonic motion was primarily affected by increases in acoustic attenuation and stiffness as the lesion formed and the interaction of these effects was complex and often counteracted each other. Further biological variability in tissue properties meant that changes in motion were masked by sample‐to‐sample variation. The HMI experiments predicted lesion formation in only about a quarter of the lesions made. In simultaneous AOI/HMI experiments it appeared that AOI was a more robust method for lesion detection. / Bernard M. Gordon Center for Subsurface and Imaging Systems (CenSSIS) via the NSF ERC award number EEC‐9986821.