The goal of this thesis is to propose and investigate a method of predicting depth of a laser dissection pulse in soft tissue without acquiring material properties of the tissue target or measuring the laser output. The method proposed is similar to what is used by laser surgical operators today, but uses regression learning to perform on-the fly predictions in place of a skilled laser surgeon. Power of the laser and the ablation depth were recorded for 57 samples and fed into the regression algorithm. Data exclusion was performed using Temperature before laser action as criteria. A linear and logarithmic model was explored using random points from the data post-exclusion, validation RMSE ranged from 135-200 micrometer. A linear and logarithmic model was explored using data points below a moving power threshold and validated with data points above said threshold, validation RMSE ranged from 108-170 micrometer. The t.test performed showed there was not a significant difference between the linear and the logarithmic models' goodness of fit metrics, but it did show there was a significant difference between the model building methods (randomly selected data points, moving power threshold). The method of building a model using lower power levels to predict larger power levels had better goodness of fit metrics than the method of selecting data points at random. In the future, this method could be used to help approximate the laser settings for surgery on a procedural basis, and allow for surgeons to perform at a higher skill level with less training.

Multifunctional theranostic nanoparticles hold promise for enabling non-invasive image guided cancer therapy such as photothermal therapy. Human breast tumor models in which response to image guided therapy can quickly and non-invasively be determined are needed to facilitate translation and application of these technologies. We hypothesize that a system utilizing a murine light-reporter mammary tumor cell line and near-infrared nanoparticles (NIR-NP) can be used to quantify response to therapy and determine fate of nanoparticles following photothermal ablation.

Marfan's syndrome is a common connective tissue disease with different musculoskeletal, ophthalmic and cardiac manifestations. Marfan's patients carry increased risk for cardiac arrhythmias. Only three cases of atrial flutter in Marfan's patients are described in the literature. We report a fourth case of a young Marfan's patient who presents with typical atrial flutter after motor vehicle accident. After electrical cardioversion, sinus rhythm was restored but he had recurrent atrial flutter on follow up. The patient then underwent electrophysiological study and successful radiofrequency catheter ablation of the flutter circuit. Since discharge, the patient has had no documented arrhythmias on follow up.

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第18086号 / 理博第3964号 / 新制||理||1571(附属図書館) / 30944 / 京都大学大学院理学研究科地球惑星科学専攻 / (主査)教授 平田 岳史, 教授 田上 高広, 准教授 三宅 亮 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20809号 / 医博第4309号 / 新制||医||1025(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 妹尾 浩, 教授 坂井 義治, 教授 戸井 雅和 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Histotripsy is a non-thermal, non-invasive, focused ultrasound ablation method that uses acoustic cavitation to mechanically break down tissues [1-8]. Histotripsy is heavily dependent on the mechanical properties of the tissue, allowing it to mechanically ablate tissues of lower mechanical stiffness while preserving the stiffer critical structures [15]. However, the mechanical properties of clinically relevant abdominal tissues and critical structures have not yet been adequately quantified under uniform testing parameters. Previous studies have tested and modeled the tissue selectivity of histotripsy, but these studies have been limited by the lack of mechanical property data available for these tissue types. In addition, there remains a need for additional experimental studies directly comparing the differential treatment doses required to induce histotripsy tissue damage in intra-abdominal tissue types. This thesis investigates the mechanical properties of intra-abdominal tissues under uniaxial tension, the effect of histotripsy treatment dose on intra-abdominal soft tissues and critical structures, and the potential of inducing damage to critical structures along the acoustic path pre-focal to the targeted histotripsy treatment. Results show that there are significant differences between the parenchymal tissues (liver, kidney) and the critical structure (stomach, gallbladder, small intestine, ducts, and vessels) elastic modulus, yield stress, yield strain, post-yield strain, energy to yield, and maximum stress and strain at yield. In general, histology analysis from the histotripsy experiments showed that there was an increase in tissue damage with increasing histotripsy pulses/point for all tissues. Critical structures with higher mechanical strength were more resistant to ablation compared to tissues with lower mechanical strength. Pre-focal studies showed damage to gallbladder and small intestine only in cases in which pre-focal cavitation was observed, while no damage occurred in skin and stomach for any samples treated at varying distances from the bubble cloud. Overall, this work improves our understanding of tissue selectivity of histotripsy and provides mechanical properties measurements for clinically relevant tissues that can be used to improve predictive models of tissue-selective histotripsy treatments. This work can be used in the planning of histotripsy treatments to establish proper margins of safety for treating intra-abdominal tumors. / Master of Science / Histotripsy is a non-invasive cancer treatment that mechanically breaks down tissues by rapidly forming and bursting bubbles within the tumor [1-8]. Histotripsy is heavily dependent on the mechanical properties of the tissue, allowing it to destroy weaker tissues while preserving the stiffer tissues in the surrounding area [15]. The mechanical properties of clinically relevant intra-abdominal tissues have not been quantified under uniform testing parameters. Previous studies have tested and modeled the tissue selectivity of histotripsy, but these studies have been limited by the mechanical property data available. This thesis investigates the mechanical properties of intra-abdominal tissues under tension, the effect of histotripsy treatment dose on intra-abdominal tissue damage, and the damage to critical structures from histotripsy treatment at varying distances from the tissue. Results show that there are significant differences between the liver and kidney mechanical stiffness and strength compared to the other tissues. In general, histology analysis showed that there is an increase in tissue damage with increasing histotripsy dose. Tissues with higher mechanical strength were more resistant to damage at lower doses compared to tissues with lower mechanical strength. Histotripsy damage to critical structures that are along the beam path, set distances in front of the focal point of the cavitation bubble cloud was studied. This study showed damage to gallbladder and small intestine only in cases in which pre-focal cavitation, cavitation bubbles that are not within the focal point of the cloud but are in contact with the tissue, was observed, while no damage occurred in skin and stomach for any samples treated at varying distances from the bubble cloud. Overall, this work improves our understanding of tissue selectivity of histotripsy and provides mechanical properties for clinically relevant tissues that can be used to improve predictive models of tissue-selective histotripsy treatments. This work can be used in the planning of histotripsy treatments to establish proper margins of safety for treating intra-abdominal tumors.

Femtosecond lasers deliver a high peak concentration of optical power while maintaining low average power. With an accompanying optical setup, this power can be focused and used for high-precision fabrication of metallized polymers via ablation, creating conductive structures on a thin film. These lasers can also be harnessed in tandem with hydrofluoric acid and the two-photon absorption principle to selectively etch silicon carbide, a very durable and machining-resistant semiconductor with desirable properties. This thesis presents improvements made to the Laser-Assisted Chemical Etching (LACE) technique and the ablation system. ��, the two- photon absorption coefficient of silicon carbide, is measured and characterized for each wafer using an optical system. The LACE etch rate of silicon carbide is found to be on average a quarter of a micrometer per 120 seconds. A new destructive imaging technique for characterizing high- aspect-ratio through-wafer non-line-of-sight features in silicon carbide is discussed, with the result of an SEM image of a LACE feature that was impossible to achieve previously. The photolithography process necessary to make use of those through-wafer features is explored. A method of leveraging image processing to maintain the focus of the laser close to the machined sample is explained, resulting in the creation of terahertz metal- mesh filters with a near one-hundred-percent success rate. It is recommended that future work explore the use of an installed confocal microscopy as a method of surface-tracking and result characterization.

Spaceborne microwave sensors are powerful tools for monitoring the impacts of global climate change on the Greenland ice sheet. This dissertation focuses on refining methods for applying microwave data in Greenland studies by using new simple theoretical and empirical models to investigate (1) azimuth anisotropies in the data, (2) the microwave signature of the snow surface, (3) detection of snow melt, and (4) classification of snow melt. The results are applicable for identifying geophysical properties of the snow surface and monitoring changes on the ice sheet in relation to melt duration/extent, accumulation, and wind patterns. Azimuth dependence of the normalized radar cross-section (sigma-0) over the Greenland ice sheet is modeled with a simple surface scattering model. The model assumes that azimuth anisotropy in 1-100 meter scale surface roughness is the primary mechanism driving the azimuth modulation. This model is inverted to estimate snow surface properties using sigma-0 measurements from the C-band European Remote Sensing Advanced Microwave Instrument (ERS) in scatterometer mode. The largest roughness estimates occur in the lower portions of the dry snow zone. Estimates of the preferential direction in surface roughness are highly correlated with katabatic wind fields over Greenland. A new observation model is introduced that uses a limited number of parameters to characterize the snow surface based on the dependence of radar backscatter on incidence angle, azimuth angle, spatial gradient, and temporal rate of change. The individual model parameters are discussed in depth with examples using data from the NASA Scatterometer (NSCAT) and from the ERS. The model may be applied for increased accuracy in scatterometer, SAR, and wide-angle SAR studies. Examples illustrating the use of the model are included with one application focusing on analysis of inter-annual change and another focusing on increased sensitivity in studies of intra-annual change. Six different melt detection method/sensor combinations are compared using data for the summer of 2000. The sensors include the Special Spectral Microwave Imager (SSM/I), SeaWinds on QuikSCAT (QSCAT), and ERS. A new method of melt detection is introduced that is based on a simple physical model relating the moisture content and depth of a layer of wet surface snow to a single channel melt detection threshold. The model can be applied to both active and passive sensors. Model-based melt estimates from different sensors are highly correlated and do not exhibit the unnatural phenomenon observed with previous methods. Trends in SSM/I channel ratios are used to differentiate subsurface and surface melt. For ablation estimation, this separation is important due to expected differences in the ablation rate for the two melt types. Evidences of the daily melt refreeze cycle are observed in the diurnal variation of the different brightness temperature channel ratios. The polarization ratio increases during periods of surface melt while the frequency ratio remains relatively constant. The frequency ratio increases during periods of expected subsurface melt. Similar trends are observed in brightness temperature measurements from in situ data collected by other investigators.

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has risen to among the top tier techniques for the direct analysis of solid samples. However, significant problems remain that must be solved to achieve the full analytical potential of LA-ICP-MS. Inefficient conversion of aerosol to ions within the ICP or transmission through the MS interface may decrease precision, sensitivity, and/or accuracy. Although fundamental mechanisms that govern ion production and transmission have been studied extensively in solution-nebulization (SN) ICP-MS instruments, significant gaps in our understanding remain. Furthermore, it is unclear to what extent differences between the aerosols generated during SN and LA influence either ion production or transmission. In this work, I initially investigated differences in the spatial distributions of Ca, Ba, and Sc ions generated by LA and SN using high-resolution LIF imaging. Ions formed from aerosol generated by LA at low fluence were distributed over much greater axial and narrower radial distances than SN aerosol. Additionally, I investigated the effects of solvent, laser fluence, and ablation atmosphere (He vs Ar) on ion distributions in the ICP. Unlike solvent, changing laser fluence and ablation atmosphere produced considerable changes in the ion signal intensity and spatial distribution during LA. At greater laser fluence, the radial distance over which ions were distributed dramatically increased. Surprisingly, when helium was mixed with argon as carrier gas, ion signals decreased. Many of these effects were assumed to be related to changes in the number and size of particles generated during LA. In a follow-up study, relative contributions to ion densities in the ICP from particles of different sizes were investigated. LIF images were recorded while filtering particles above a threshold size on-line. Micron-sized particles contributed the majority of ions formed in the ICP. For Ba, Ca, and Sc, differences in the axial position where nanometer- and micron-sized particles vaporized were 2, 1, and less than 1 mm, respectively. I also performed experiments to identify changes in the ion signal related to changing ablation conditions vs. changing ICP conditions associated with helium additions to the carrier gas. LIF images were recorded during different combinations of He/Ar added upstream and/or downstream of the ablation cell. Changes in the ion signal during ablation in helium vs argon did not always match expectations based on changes in particle numbers and sizes measured with SEM. The results force re-examination of some of the fundamental assumptions about the effect of carrier gas composition on the performance of LA-ICP-MS. The research described in this dissertation provides valuable insight into fundamental aspects of key ICP processes related to LA generated aerosol.