Focused ultrasound (FUS) is an emerging technology, and it plays an essential role in clinical and contactless acoustic energy transfer applications. These applications have critical criteria for the acoustic pressure level, the creation of complex pressure patterns, spatial management of the complicated acoustic field, and the degree of nonlinear waveform distortion at the focal areas, which have not been met to date. This dissertation focuses on introducing experimentally validated novel numerical approaches, optimization algorithms, and experimental techniques to fill existing knowledge gaps and enhance the functionality of holographic acoustic lenses (HALs) with an emphasis on applications related to biomedical-focused ultrasound and ultrasonic energy transfer. This dissertation also aims to investigate the dynamics of nonlinear acoustic beam shaping in engineered HALs. First, We will introduce 3D-printed metallic acoustic holographic mirrors for precise spatial manipulation of reflected ultrasonic waves. Optimization algorithms and experimental validations are presented for applications like contactless acoustic energy transfer. Furthermore, a portion of the present work focuses on designing holographic lenses in strongly heterogeneous media for ultrasound focusing and skull aberration compensation in transcranial-focused ultrasound. To this end, we collaborated with the Biomedical Engineering and Mechanics Department as well as Fralin Biomedical Research Institute to implement acoustic lenses in transcranial neuromodulation, targeting to improve the quality of life for patients with brain disease by minimizing the treatment time and optimizing the ultrasonic energy into the region of interest. We will also delve into the nonlinear regime for High-Intensity Focused Ultrasound (HIFU) applications, this study is structured under three objectives: (1) establishing nonlinear acoustic-elastodynamics models to represent the dynamics of holographic lenses under low- to high-intensity acoustic fields; (2) validating and leveraging the resulting models for high-fidelity lens designs used in generating specified nonlinear ultrasonic fields of complex spatial distribution; (3) exploiting new physical phenomena in acoustic holography. The performed research in this dissertation yields experimentally proven mathematical frameworks for extending the functionality of holographic lenses, especially in transcranial-focused ultrasound and nonlinear wavefront shaping, advancing knowledge in the burgeoning field of the inverse issue of nonlinear acoustics, which has remained underdeveloped for many years. / Doctor of Philosophy / Ultrasonic waves are sound waves that have frequencies higher than the upper audible limit of human hearing. The versatility and non-invasive nature of ultrasonic waves make them a valuable tool in numerous scientific, medical, and industrial applications. In healthcare, ultrasonic waves are employed in diagnostic imaging techniques, such as ultrasound scans, to create images of internal body structures. Ultrasonic waves are also used for non-destructive testing (NDT) of materials, detecting flaws or cracks within structures without causing any damage. Furthermore, this technology finds applications in the field of material science for the manipulation of particles and in biomedical research for drug delivery systems. Focused ultrasound sound is an emerging non-invasive therapeutic modality that uses focused ultrasound waves to target tissue within the body without damaging the surrounding tissue. This technology allows for precise delivery of ultrasound energy to a specific region, where it can induce various desired therapeutic effects depending on the targeting location and parameters. Therapeutic focused ultrasound has the advantage of being non-invasive, reducing the risks and recovery time associated with traditional surgery. It can be precisely controlled and monitored in real-time with imaging techniques such as ultrasound or MRI, ensuring the targeted treatment of pathological tissues while sparing healthy ones. Applications of therapeutic are broad and include tumor ablation, facilitation of drug delivery across the blood-brain barrier, relief of chronic pain, and treatment of essential tremor and other neurological disorders. The domain of therapeutic focused ultrasound is continually advancing, driven by research that seeks to extend its applications. Recent developments in acoustic engineering and 3D printing have led to the creation of acoustic holograms, or holographic acoustic lenses, which allow for more refined control over the spatial structure of the acoustic field. These technological advancements hold the promise of enhancing FUS by improving the accuracy of acoustic field localization and providing a more cost-effective solution compared to conventional systems like phased array transducers. However, the accuracy and applicability of existing models and techniques are constrained by assumptions, including the uniformity of the propagation medium and the linearity of the acoustic field, which limits the functionality and restricts the potential applications of acoustic holograms. In this dissertation, we present novel numerical techniques, algorithms, and proof-of-concept experiments to fill those knowledge gaps and expand the functionality of acoustic holograms in crucial applications.

Thesis (MSc)--Stellenbosch University, 2001. / ENGLISH ABSTRACT: In response to increased focus on schemas within cognitive therapy and specifically in the treatment of personality disorders, Young developed an instrument to measure early maladaptive schemas, the Young Schema Questionnaire (YSQ). The statistical properties of this measure have been investigated, and due to its length, a shortened version was developed (the YSQ-S). In the present study the factor structure of the YSQ-S was investigated in a group of South African undergraduate psychology students (N = 300). In contrast with the findings of the studies done on the YSQ, 14 of Young's 15 schemas were identified as factors in the YSQ-S, corresponding largely with the theoretically underlying structure. A higher order factor analysis solution was also found to resemble the structure proposed by Young. / AFRIKAANSE OPSOMMING: Die groter fokus op skemas binne die kognitiewe terapie, veral met betrekking tot die behandeling van persoonlikheidsversteurings, het daartoe gelei dat Young 'n meetmiddel, naamlik die Young Schema Questionnaire (YSQ), ontwikkel het om vroeë wanaangepaste skemas ("early maladaptive schemas") te meet. Die statistiese eienskappe van hierdie meetmiddel is reeds nagevors, en as gevolg van die lengte van hierdie meetmiddel, is 'n verkorte weergawe daarvan ontwikkel (YSQ-S). In die huidige studie is die faktoriale struktuur van die YSQ-S by 'n groep Suid Afrikaanse voorgraadse sielkunde studente (N = 300) ondersoek. In teenstelling met die bevindings van vroeëre studies op die YSQ, is 14 van die 15 van Young se skemas as faktore by die YSQ-S geïdentifiseer, wat grootliks ooreengestem het met die teoreties gekonseptualiseerde onderligende struktuur. Die oplossing van 'n hoër-ordefaktorontleding het ook ooreengestem met die struktuur wat deur Young voorgestel is.

published_or_final_version / Social Work / Master / Master of Social Work

Spatio-temporal variability in groundwater discharge and contaminant fluxes along a channelized stream in western Kentucky Surface and groundwater discharges and contaminant fluxes can vary with time and space depending upon the hydrogeological processes and geological setting of the area of interest. This study examined a ~300-m-long, channelized reach of a first-order perennial stream, Little Bayou Creek, in the Coastal Plain of far western Kentucky during the period October 2010–February 2012. Along the study reach, springs discharge groundwater contaminated by the chlorinated organic compound trichloroethene (TCE) and radionuclide technetium-99 (99Tc) released as a result of past activities at the U.S. Department of Energy’s Paducah Gaseous Diffusion Plant. The study addressed variability in groundwater discharge patterns and contaminant concentrations at various timescales (seasonal, annual, and decadal) and the extent to which the discharge sites are spatially persistent. Understanding patterns of groundwater discharge along a stream can be important for assessing the fate and transport of aqueous contaminants. Groundwater discharge was estimated during baseflow conditions using different mass-balance approaches, including velocity-area and dye-dilution gauging. Discharge fluctuated seasonally but typically increased downstream, indicating the entire study reach to be gaining throughout the year. Discharge rates of individual springs also fluctuated seasonally. Tracer test data were utilized to model flow and transient storage along the reach using the USGS software OTIS-P. Cross-sectional area determined from OTIS-P was similar to that measured by velocity-area gauging. Reach area-normalized discharge fluxes were comparable to values determined by Darcy’s law calculations from a pair of monitoring wells at the downstream end of the study reach. Temperature data acquired from probing along grids in winter and summer, from fiber-optic sensing along the reach in autumn, and from data-loggers and manual measurements in springs were used to delineate focused discharge locations. Comparison of temperature-probing results with prior studies indicated that locations of some springs persisted over a decade, whereas other springs emerged and disappeared. Because the stream is located in unlithified sediments, discharge rates of springs appear to fluctuate with soil piping and collapse along joints in fractured clay. Contaminant concentrations in springs decreased downstream along the reach and were lower than observed during September 1999 – May 2001. The continued occurrence of dissolved oxygen and the absence of TCE daughter products in springs suggest that the decrease in TCE concentrations resulted from the installation of upgradient extraction wells, rather than from intrinsic reductive degradation. KEYWORDS: Contaminant fluxes, trichloroethene, technetium-99, baseflow, temperature probing.

In two studies, this thesis depicts the relationship between minority group status in the United States, perceived discrimination, and coping with stress. Past literature on coping and its types – problem-focused versus emotion-focused – is inconsistent in terms of differences between minority status groups and majority groups. It remains unknown whether or why Black Americans and lesbian or gay Americans may demonstrate coping patterns that differ from White Americans and heterosexual Americans, respectively. What is altogether absent from the literature is the possible mediating factor of perceived discrimination experienced by these minority groups. That is, differences in internal, stable coping processes that manage stress may have been molded by one’s experience with discrimination. Study 1 examines the relationship between race (Black versus White) and coping, mediated by perceived discrimination. Study 2 examines the relationship between sexual orientation (lesbian or gay versus heterosexual) and coping, mediated by perceived discrimination. Both studies confirm the thesis that minority group members exhibit maladaptive, emotion-focused coping more than majority group members – but that this difference is explained by the minority group members’ perceived discrimination. Historical and political relevance, social implications, and possible limitations in design and interpretation are discussed. / text

This study investigated the effects of two novel forms of 8-week mindfulness meditation training, focused attention (FA) and open monitoring (OM), relative to an established training, mindfulness-based cognitive therapy (MBCT), on early emotional reactivity to negative emotional images as assessed by electroencephalography (EEG). Data on the late-positive potential (LPP) were analyzed to address whether the three mindfulness interventions attenuated the LPP from pre- to post-intervention, and if significant differences existed between groups in LPP at post-intervention. Rather than an attenuation, results indicated an average increase in LPP amplitude from pre- to post-intervention. No significant differences were found in the LPP between the training conditions at post-intervention. These results provide preliminary evidence that mindfulness training in novice practitioners may heighten initial emotional reactivity. Further, well-designed research is needed to examine a wider range of neural responses to better understand emotion regulation process effects of different forms of mindfulness training.

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.

The problem with which this study is concerned is a comparison of the effects of three methods of focused feedback upon selected client behaviors in individual counseling. This study has a twofold purpose. The first is to examine which of three methods of focused feedback (videotape, audiotape, or verbal) is most effective in producing selected behavioral changes in clients seen in individual counseling. The second is to compare the effects of the three methods of focused feedback on individual clients with the effects of a traditional individual counseling approach that did not utilize focused feedback.

Thesis advisor: Cyril P. Opeil / The physiology of the vasculature in the central nervous system (CNS) which includes the blood-brain-barrier (BBB) and other factors, prevents the transport of most anticancer agents to the brain and restricts delivery to infiltrating brain tumors. The heterogeneous vascular permeability in tumor vessels (blood-tumor barrier; BTB), along with several other factors, creates additional hurdles for drug treatment of brain tumors. Different methods have been used to bypass the BBB/BTB, but they have their own limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Magnetic Resonance Imaging guided Focused Ultrasound (MRIgFUS), when combined with circulating microbubbles, is an emerging noninvasive method to temporarily permeabilize the BBB and BTB. The purpose of this thesis was to use this alternative approach to deliver chemotherapeutic agents through the BBB/BTB for brain tumor treatment in a rodent model to overcome the hinderances encountered in prior approaches tested for drug delivery in the CNS. The results presented in thesis demonstrate that MRIgFUS can be used to achieve consistent and reproducible BBB/BTB disruption in rats. It enabled us to achieve clinically-relevant concentrations of doxorubicin (~ 4.8±0.5 µg/g) delivered to the brain with the sonication parameters (0.69 MHz; 0.55 MPa; 10 ms bursts; 1 Hz PRF; 60 s duration), microbubble concentration (Definity, 10 µl/kg), and liposomoal doxorubicin (Lipo-DOX) dose (5.67 mg/kg) used. The resulting doxorubicin concentration was reduced by 32% when the agent was injected 10 minute after the last sonication. Three weekly sessions of FUS and Lipo-DOX appeared to be safe in the rat brain, despite some minor tissue damage. Importantly, the severe neurotoxicity seen in earlier works using other approaches does not appear to occur with delivery via FUS-BBB disruption. The resuls from three weekly treatments of FUS and Lipo-DOX in a rat glioma model are highly promising since they demonstrated that the method significantly inhibits tumor growth and improves survival. Animals that received three weekly sessions of FUS + Lipo-DOX (N = 8) had a median survival time that was increased significantly (P<0.001) compared to animals who received Lipo-DOX only (N = 6), FUS only (N = 8), or no treatment (N = 7). Median survival for animals that received FUS + Lipo-DOX was increased by 100% relative to untreated controls, whereas animals who received Lipo-DOX alone had only a 16% improvement. Animals who received only FUS showed no improvement. No tumor cells were found in histology in 4/8 animals in the FUS + Lipo-DOX group, and only a few tumor cells were detected in two animals. Tumor doxorubicin concentrations increased monotonically (823±600, 1817±732 and 2432±448 ng/g) in the control tumors at 9, 14 and 17 days respectively after administration of Lipo-DOX. With FUS-induced BTB disruption, the doxorubicin concentrations were enhanced significantly (P<0.05, P<0.01, and P<0.0001 at days 9, 14, and 17, respectively) and were greater than the control tumors by a factor of two or more (2222±784, 3687±796 and 5658±821 ng/g) regardless of the stage of tumor growth. The transfer coefficient Ktrans was significantly (p<0.05) enhanced compared to control tumors only at day 9 but not at day 14 or 17. These results suggest that FUS-induced enhancements in tumor drug delivery for Lipo-DOX are relatively consistent over time, at least in this tumor model. These results are encouraging for the use of large drug carriers, as they suggest that even large/late-stage tumors can benefit from FUS-induced drug enhancement. Corresponding enhancements in Ktrans were found variable in large/late-stage tumors and not significantly different than controls, perhaps reflecting the size mismatch between the liposomal drug (~100 nm) and Gd-DTPA (molecular weight: 938 Da). Overall, this thesis research provides pre-clinical data toward the development of MRIgFUS as a noninvasive method for the delivery of agents such as Lipo-DOX across the BBB/BTB to treat patients with diseases of the central nervous system. / Thesis (PhD) — Boston College, 2014. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Physics.

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.