Abordagem da piezocirurgia na Medicina Dentária

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária

INVESTIGATION OF BUBBLE DYNAMICS AND HEATING DURING FOCUSED ULTRASOUND INSONATION IN TISSUE-MIMICKING MATERIALS

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.

Quantitative Particle Characterization by Scattered Ultrasound

The topic of this thesis is an acoustic scattering technique for detennining the compressibility and density of individual particles. The particles, which have diameters on the order of 10 µm, are modeled as fluid spheres. Ultrasonic tone bursts of 2 µsec duration and 30 MHz center frequency scatter from individual particles as they traverse the focal region of two confocally positioned transducers. One transducer acts as a receiver while the other both transmits and receives acoustic signals. The resulting scattered bursts are detected at 90° and at 180° (backscattered). Using either the long wavelength (Rayleigh) or the weak scatterer (Born) approximations, it is possible to detennine the compressibility and density of the particle provided we possess a priori knowledge of the particle size and the host properties. The detected scattered signals are digitized and stored in computer memory. With this information we can compute the mean compressibility and density averaged over a population of particles ( typically 1000 particles) or display histograms of scattered amplitude statistics. An experiment was run first run to assess the feasibility of using polystyrene polymer microspheres to calibrate the instrument. A second study was performed on the buffy coat harvested from whole human blood. Finally, chinese hamster ovary cells which were subject to hyperthermia treatment were studied in order to see if the instrument could detect heat induced membrane blebbing.

Development of large-scale colloidal crystallisation methods for the production of photonic crystals

Colloidal photonic crystals have potential light manipulation applications including; fabrication of efficient lasers and LEDs, improved optical sensors and interconnects, and improving photovoltaic efficiencies. One road-block of colloidal selfassembly is their inherent defects; however, they can be manufactured cost effectively into large area films compared to micro-fabrication methods. This thesis investigates production of ‘large-area’ colloidal photonic crystals by sonication, under oil co-crystallization and controlled evaporation, with a view to reducing cracking and other defects. A simple monotonic Stöber particle synthesis method was developed producing silica particles in the range of 80 to 600nm in a single step. An analytical method assesses the quality of surface particle ordering in a semiquantitative manner was developed. Using fast Fourier transform (FFT) spot intensities, a grey scale symmetry area method, has been used to quantify the FFT profiles. Adding ultrasonic vibrations during film formation demonstrated large areas could be assembled rapidly, however film ordering suffered as a result. Under oil cocrystallisation results in the particles being bound together during film formation. While having potential to form large areas, it requires further refinement to be established as a production technique. Achieving high quality photonic crystals bonded with low concentrations (<5%) of polymeric adhesives while maintaining refractive index contrast, proved difficult and degraded the film’s uniformity. A controlled evaporation method, using a mixed solvent suspension, represents the most promising method to produce high quality films over large areas, 75mm x 25mm. During this mixed solvent approach, the film is kept in the wet state longer, thus reducing cracks developing during the drying stage. These films are crack-free up to a critical thickness, and show very large domains, which are visible in low magnification SEM images as Moiré fringe patterns. Higher magnification reveals separation between alternate fringe patterns are domain boundaries between individual crystalline growth fronts.

Preclinical atherosclerosis in rheumatoid arthritis

Introduction: There is accumulating evidence of an increased risk of cardiovascular morbidity and mortality in rheumatoid arthritis patients. A combination of both traditional cardiovascular risks and rheumatoid specific factors appear to be responsible for driving this phenomenon. Rheumatoid arthritis has been an orphan of cardiologists in the past and rheumatologists themselves are not good at CVD screening. Identifying the extent of preclinical atherosclerosis in RA patients will help us to appreciate the magnitude of this serious problem in an Irish population. Methods: We undertook a cross-sectional study of 63 RA patients and 48 OA controls and compared the 2 groups with respect to 1) traditional CV risks factors, 2) serum biomarkers of inflammation, including CRP, TNFα, IL6 and PAI-1, 3) carotid intima-media thickness (cIMT), carotid plaque and ankle-brachial index (ABI) as markers of pre-clinical atherosclerosis, 4) biochemical and ultrasonic measures of endothelial dysfunction and 5) serum and echocardiographic measures of diastolic dysfunction. Within the RA group, we also investigated for associations between markers of inflammation, subclinical atherosclerosis and diastolic dysfunction. Results: Prevalence of traditional CV risks was similar in the RA and OA groups. A number of biomarkers of inflammation were significantly higher in the RA group: CRP, fibrinogen, IL- 2, -4, -6, TNFα. PAI-1, a marker of thrombosis, correlated with disease activity and subclinical atherosclerosis in RA patients. With regard to subclinical atherosclerosis measures, RA patients had a significantly lower ABI than OA patients. Carotid plaque and cIMT readings were similar in RA and OA patients. Assessment of endothelial function revealed that RA patients had significantly higher concentrations of adhesion molecules, in particular sero-positive RA patients and RA smokers. Adhesion molecule concentrations were associated with markers of diastolic dysfunction in RA. Urine PCR, another marker of endothelial dysfunction also correlated with diastolic dysfunction in RA. Assessment of endothelial function with flow mediated dilatation (FMD) found no difference between the RA and OA groups. Disease activity scores in RA patients were associated with endothelial dysfunction, as assessed by FMD. Conclusions: We did not find significant differences in measures of subclinical atherosclerosis, flow mediated dilatation or diastolic function between RA and OA patients. This is most likely in part due to the fact that there is increasing evidence that OA has an inflammatory component to its pathogenesis and is associated with metabolic syndrome and increased CV risk. We reported a significant association between urinary PCR and measures of diastolic dysfunction. Urinary PCR may be a useful screening tool for diastolic dysfunction in RA. The association between RA disease activity and measures of vascular function supports the theory that the excess cardiovascular burden in RA is linked to uncontrolled inflammation.

Atomic layer deposition of interface control layers for the fabrication of III/V MOS devices

The continued advancement of metal oxide semiconductor field effect transistor (MOSFET) technology has shifted the focus from Si/SiO2 transistors towards high-κ/III-V transistors for high performance, faster devices. This has been necessary due to the limitations associated with the scaling of the SiO2 thickness below ~1 nm and the associated increased leakage current due to direct electron tunnelling through the gate oxide. The use of these materials exhibiting lower effective charge carrier mass in conjunction with the use of a high-κ gate oxide allows for the continuation of device scaling and increases in the associated MOSFET device performance. The high-κ/III-V interface is a critical challenge to the integration of high-κ dielectrics on III-V channels. The interfacial chemistry of the high-κ/III-V system is more complex than Si, due to the nature of the multitude of potential native oxide chemistries at the surface with the resultant interfacial layer showing poor electrical insulating properties when high-κ dielectrics are deposited directly on these oxides. It is necessary to ensure that a good quality interface is formed in order to reduce leakage and interface state defect density to maximise channel mobility and reduce variability and power dissipation. In this work, the ALD growth of aluminium oxide (Al2O3) and hafnium oxide (HfO2) after various surface pre-treatments was carried out, with the aim of improving the high-κ/III-V interface by reducing the Dit – the density of interface defects caused by imperfections such as dangling bonds, dimers and other unsatisfied bonds at the interfaces of materials. A brief investigation was performed into the structural and electrical properties of Al2O3 films deposited on In0.53Ga0.47As at 200 and 300oC via a novel amidinate precursor. Samples were determined to experience a severe nucleation delay when deposited directly on native oxides, leading to diminished functionality as a gate insulator due to largely reduced growth per cycle. Aluminium oxide MOS capacitors were prepared by ALD and the electrical characteristics of GaAs, In0.53Ga0.47As and InP capacitors which had been exposed to pre-pulse treatments from triethyl gallium and trimethyl indium were examined, to determine if self-cleaning reactions similar to those of trimethyl aluminium occur for other alkyl precursors. An improved C-V characteristic was observed for GaAs devices indicating an improved interface possibly indicating an improvement of the surface upon pre-pulsing with TEG, conversely degraded electrical characteristics observed for In0.53Ga0.47As and InP MOS devices after pre-treatment with triethyl gallium and trimethyl indium respectively. The electrical characteristics of Al2O3/In0.53Ga0.47As MOS capacitors after in-situ H2/Ar plasma treatment or in-situ ammonium sulphide passivation were investigated and estimates of interface Dit calculated. The use of plasma reduced the amount of interface defects as evidenced in the improved C-V characteristics. Samples treated with ammonium sulphide in the ALD chamber were found to display no significant improvement of the high-κ/III-V interface. HfO2 MOS capacitors were fabricated using two different precursors comparing the industry standard hafnium chloride process with deposition from amide precursors incorporating a ~1nm interface control layer of aluminium oxide and the structural and electrical properties investigated. Capacitors furnished from the chloride process exhibited lower hysteresis and improved C-V characteristics as compared to that of hafnium dioxide grown from an amide precursor, an indication that no etching of the film takes place using the chloride precursor in conjunction with a 1nm interlayer. Optimisation of the amide process was carried out and scaled samples electrically characterised in order to determine if reduced bilayer structures display improved electrical characteristics. Samples were determined to exhibit good electrical characteristics with a low midgap Dit indicative of an unpinned Fermi level

Boosting high-intensity focused ultrasound-induced anti-tumor immunity using a sparse-scan strategy that can more effectively promote dendritic cell maturation.

BACKGROUND: The conventional treatment protocol in high-intensity focused ultrasound (HIFU) therapy utilizes a dense-scan strategy to produce closely packed thermal lesions aiming at eradicating as much tumor mass as possible. However, this strategy is not most effective in terms of inducing a systemic anti-tumor immunity so that it cannot provide efficient micro-metastatic control and long-term tumor resistance. We have previously provided evidence that HIFU may enhance systemic anti-tumor immunity by in situ activation of dendritic cells (DCs) inside HIFU-treated tumor tissue. The present study was conducted to test the feasibility of a sparse-scan strategy to boost HIFU-induced anti-tumor immune response by more effectively promoting DC maturation. METHODS: An experimental HIFU system was set up to perform tumor ablation experiments in subcutaneous implanted MC-38 and B16 tumor with dense- or sparse-scan strategy to produce closely-packed or separated thermal lesions. DCs infiltration into HIFU-treated tumor tissues was detected by immunohistochemistry and flow cytometry. DCs maturation was evaluated by IL-12/IL-10 production and CD80/CD86 expression after co-culture with tumor cells treated with different HIFU. HIFU-induced anti-tumor immune response was evaluated by detecting growth-retarding effects on distant re-challenged tumor and tumor-specific IFN-gamma-secreting cells in HIFU-treated mice. RESULTS: HIFU exposure raised temperature up to 80 degrees centigrade at beam focus within 4 s in experimental tumors and led to formation of a well-defined thermal lesion. The infiltrated DCs were recruited to the periphery of lesion, where the peak temperature was only 55 degrees centigrade during HIFU exposure. Tumor cells heated to 55 degrees centigrade in 4-s HIFU exposure were more effective to stimulate co-cultured DCs to mature. Sparse-scan HIFU, which can reserve 55 degrees-heated tumor cells surrounding the separated lesions, elicited an enhanced anti-tumor immune response than dense-scan HIFU, while their suppressive effects on the treated primary tumor were maintained at the same level. Flow cytometry analysis showed that sparse-scan HIFU was more effective than dense-scan HIFU in enhancing DC infiltration into tumor tissues and promoting their maturation in situ. CONCLUSION: Optimizing scan strategy is a feasible way to boost HIFU-induced anti-tumor immunity by more effectively promoting DC maturation.

Environmental management for malaria control: knowledge and practices in Mvomero, Tanzania.

Environmental conditions play an important role in the transmission of malaria; therefore, regulating these conditions can help to reduce disease burden. Environmental management practices for disease control can be implemented at the community level to complement other malaria control methods. This study assesses current knowledge and practices related to mosquito ecology and environmental management for malaria control in a rural, agricultural region of Tanzania. Household surveys were conducted with 408 randomly selected respondents from 10 villages and qualitative data were collected through focus group discussions and in-depth interviews. Results show that respondents are well aware of the links between mosquitoes, the environment, and malaria. Most respondents stated that cleaning the environment around the home, clearing vegetation around the home, or draining stagnant water can reduce mosquito populations, and 63% of respondents reported performing at least one of these techniques to protect themselves from malaria. It is clear that many respondents believe that these environmental management practices are effective malaria control methods, but the actual efficacy of these techniques for controlling populations of vectors or reducing malaria prevalence in the varying ecological habitats in Mvomero is unknown. Further research should be conducted to determine the effects of different environmental management practices on both mosquito populations and malaria transmission in this region, and increased participation in effective techniques should be promoted.

Male mice song syntax depends on social contexts and influences female preferences.

In 2005, Holy and Guo advanced the idea that male mice produce ultrasonic vocalizations (USV) with some features similar to courtship songs of songbirds. Since then, studies showed that male mice emit USV songs in different contexts (sexual and other) and possess a multisyllabic repertoire. Debate still exists for and against plasticity in their vocalizations. But the use of a multisyllabic repertoire can increase potential flexibility and information, in how elements are organized and recombined, namely syntax. In many bird species, modulating song syntax has ethological relevance for sexual behavior and mate preferences. In this study we exposed adult male mice to different social contexts and developed a new approach of analyzing their USVs based on songbird syntax analysis. We found that male mice modify their syntax, including specific sequences, length of sequence, repertoire composition, and spectral features, according to stimulus and social context. Males emit longer and simpler syllables and sequences when singing to females, but more complex syllables and sequences in response to fresh female urine. Playback experiments show that the females prefer the complex songs over the simpler ones. We propose the complex songs are to lure females in, whereas the directed simpler sequences are used for direct courtship. These results suggest that although mice have a much more limited ability of song modification, they could still be used as animal models for understanding some vocal communication features that songbirds are used for.

Direct measurement of powder flavour adhesion on to a food surface using a novel adhesion tester

The firm adhesion of flavouring particles onto crisp surfaces during coating processes is a major concern in the snack production industry. Detachment of flavouring powders from products during handling and production stages can lead to substantial financial losses for the industry, in terms of variable flavour performance and extended cleaning down time of fugitive particle build-up on process equipment. Understanding the adhesion strength of applied bulk particulates used for flavouring formulations will help analysts to evaluate the efficiency of coating processes and potentially enable them to assess the adhesion strength of newly formulated flavouring powder prior to commitment to full scale plant trials. A rapid prototype of a novel adhesion tester has been designed and constructed. The apparatus operates according to the principle of impact force acting on particles attached to the surface of the food substrate. The main component is a circular plate to which four sample holders are attached and which is subjected to vertical travel down a guide shaft. Several flavouring powders have been tested extensively. By plotting the detachment versus impact force, the difference obtained between adhesion strength of different flavouring powders (which is a strong function of particle size) has been discussed.

Towards An Acoustic Model-Based Poroelastic Imaging Method: I. Theoretical Foundation

The ultrasonic measurement and imaging of tissue elasticity is currently under wide investigation and development as a clinical tool for the assessment of a broad range of diseases, but little account in this field has yet been taken of the fact that soft tissue is porous and contains mobile fluid. The ability to squeeze fluid out of tissue may have implications for conventional elasticity imaging, and may present opportunities for new investigative tools. When a homogeneous, isotropic, fluid-saturated poroelastic material with a linearly elastic solid phase and incompressible solid and fluid constituents is subjected to stress, the behaviour of the induced internal strain field is influenced by three material constants: the Young's modulus (E(s)) and Poisson's ratio (nu(s)) of the solid matrix and the permeability (k) of the solid matrix to the pore fluid. New analytical expressions were derived and used to model the time-dependent behaviour of the strain field inside simulated homogeneous cylindrical samples of such a poroelastic material undergoing sustained unconfined compression. A model-based reconstruction technique was developed to produce images of parameters related to the poroelastic material constants (E(s), nu(s), k) from a comparison of the measured and predicted time-dependent spatially varying radial strain. Tests of the method using simulated noisy strain data showed that it is capable of producing three unique parametric images: an image of the Poisson's ratio of the solid matrix, an image of the axial strain (which was not time-dependent subsequent to the application of the compression) and an image representing the product of the aggregate modulus E(s)(1-nu(s))/(1+nu(s))(1-2nu(s)) of the solid matrix and the permeability of the solid matrix to the pore fluid. The analytical expressions were further used to numerically validate a finite element model and to clarify previous work on poroelastography.

Complex weathering in drylands: implications of 'stress' history for rock debris breakdown and sediment release

Weathering studies have often sought to explain features in terms of a prevailing set of environmental conditions. However, it is clear that in most present-day hot desert regions, the surface rock debris has been exposed to a range of weathering environments and processes. These different weathering conditions can arise in two ways, either from the effects of long-term climate change acting on debris that remains relatively static within the landscape or through the spatial relocation of debris from high to low altitude. Consequently, each fragment of rock may contain a unique weathering-related legacy of damage and alteration — a legacy that may greatly influence its response to present-day weathering activity. Experiments are described in which blocks of limestone, sandstone, granite and basalt are given ‘stress histories’ by subjecting them to varying numbers of heating and freezing cycles as a form of pre-treatment. These imposed stress histories act as proxies for a weathering history. Some blocks were used in a laboratory salt weathering simulation study while others underwent a 2 year field exposure trial at high, mid and low altitude sites in Death Valley, California. Weight loss and ultrasonic pulse velocity measurements suggest that blocks with stress histories deteriorate more rapidly than unstressed samples of the same rock type exposed to the same environmental conditions. Laboratory data also indicate that the result of imposing a known ‘weathering history’ on samples by pre-stressing them is an increase in the amount of fine sediment released during salt weathering over a given period of time in comparison to unstressed samples.

Electroreduction of N-methylphthalimide in room temperature ionic liquids under insonated and silent conditions

The selective electroreduction N-methylphthalimide to 3-hydroxy-2-methyl-isoindolin-1-one has been performed in ionic liquids using phenol as a proton donor under silent and ultrasonic conditions. A significant increase in the rate of electroreduction is shown using ultrasonic activation and in addition high current efficiencies were observed. Some decomposition of the ionic liquid was found to have occurred under exposure to ultrasound. © 2004 Elsevier B.V. All rights reserved.

Solvation of 1-butyl-3-methylimidazolium hexafluorophosphate in aqueous ethanol - a green solution for dissolving 'hydrophobic' ionic liquids

The relatively hydrophobic ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate has been found to be totally miscible with aqueous ethanol between 0.5 and 0.9 mol fraction ethanol, whereas the ionic liquid is only partially miscible with either pure water or absolute ethanol; the ability to dissolve 1-butyl-3-methylimidazolium hexafluorophosphate in a 'green' aqueous solvent system has important implications for cleaning, purification, and separations using ionic liquids.