With the introduction of four dimensional-computed tomography (4DCT), treatment centers are now better able to account for respiration-induced uncertainty in radiation therapy treatment planning for lung cancer. We examined two practices in which 4DCT is used in radiotherapy. Our first study investigated the dosimetric uncertainty in four-dimensional (4D) dose calculation using three temporal probability distributions: 1) uniform distribution, 2) sinusoidal distribution, and 3) patient-specific distribution derived from the respiratory trace. Four-dimensional dose was evaluated in nine lung cancer patients. First, dose was computed for each of 10 binned CTs using 4DCT and deformable image registration. Next, the 10 deformed doses were summed together using one of three temporal probability distributions. To compare the two approximated 4D dose calculations to the 4D calculation derived using the patient's respiratory trace, 3D gamma analysis was performed using a tolerance criteria of 3% dose difference and 3mm distance to agreement. Additionally, mean lung dose (MLD), mean tumor dose (MTD), and lung V20 were used to assess clinical impact. For all patients, both uniform and sinusoidal dose distributions were found to have an average gamma passing rate >99% for both the lung and PTV volumes. Compared with 4D dose calculated using the patient respiratory trace, uniform distribution and sinusoidal distribution showed a percentage difference on average of -0.1±0.6% and -0.2±0.4% in MTD, -0.2±2.0% and -0.2±1.3% in MLD, 0.9±2.8% and -0.7±1.8% in lung V20, respectively. We concluded that 4D dose computed using either a uniform or sinusoidal temporal probability distribution is able to approximate 4D dose computed using the patient-specific respiratory trace. Our second study evaluated the dosimetric and temporal effects of respiratory gated radiation therapy using four different gating windows (20EX-20IN, 40EX-40IN, 60EX-60IN, and 80EX-80IN) and estimated the corresponding treatment delivery times for normal (500MU/min) and high (1500MU/min) dose rates. Five patients (3 non-gated, 2 gated 80EX-80IN) were retrospectively evaluated. For each patient, four individual treatment plans corresponding to the four different gating windows were created, and treatment delivery time for each plan was estimated using a MATLAB (MathWorks, Natick, MA) algorithm. Results showed that smaller gating windows reduced PTV volume, mean lung dose, and lung V20, while maintaining mean tumor dose and PTV coverage. Treatment times for gated plans were longer when dose rate was unchanged, however, increased dose rates were shown to achieve treatment times comparable to or faster than non-gated delivery times. We concluded that gated radiation therapy in lung cancer patients could potentially reduce lung toxicity, while as effectively treating the target volume. Furthermore, increased dose rates with gated radiation therapy are able to provide treatment times comparable to non-gated treatment.

In this dissertation, I utilize digital holographic microscopy (DHM) to study the motility of biological cells. As an important feature of DHM, quantitative phase microscopy by digital holography (DH-QPM) is applied to study the cell-substrate interactions and migratory behavior of adhesive cells. The traction force exerted by biological cells is visualized as distortions in flexible substrata. Motile fibroblasts produce wrinkles when attached to a silicone rubber film. For the non-wrinkling elastic substrate polyacrylamide (PAA), surface deformation due to fibroblast adhesion and motility is visualized as tangential and vertical displacement. This surface deformation and the associated cellular traction forces are measured from phase profiles based on the degree of distortion. Intracellular fluctuations in amoeba cells are also analyzed statistically by DH-QPM. With the capacity of yielding quantitative measures directly, DH-QPM provides efficient and versatile means for quantitative analysis of cellular or intracellular motility. Three-dimensional profiling and tracking by DHM enable label-free and quantitative analysis of the characteristics and dynamic processes of objects, since DHM can record real-time data for micro-scale objects and produce a single hologram containing all the information about their three-dimensional structure. Here, I utilize DHM to visualize suspended microspheres and microfibers in three dimensions, and record the four-dimensional trajectories of free-swimming cells in the absence of mechanical focus adjustment. The displacement of microfibers due to interactions with cells in three spatial dimensions is measured as a function of time at sub-second and micrometer levels in a direct and straightforward manner. It has thus been shown that DHM is a highly efficient and versatile means for quantitative tracking and analysis of cell motility.

<p>Imaging respiratory induced tumor motion in the radiation therapy treatment room could eliminate the necessity for large motion encompassing margins that result in excessive irradiation of healthy tissues. Currently available image guidance technologies are ill-suited for this task. Two-dimensional fluoroscopic images are acquired with sufficient speed to image respiratory motion. However, volume information is not present, and soft tissue structures are often not visible because a large volume is projected onto a single plane. Currently available volumetric imaging modalities are not acquired with sufficient speed to capture full motion trajectory information. Four-dimensional cone-beam computed tomography (4D CBCT) using a gantry mounted 2D flat panel imaging device has been proposed but has been limited by high doses, long scan times and severe under-sampling artifacts. The focus of the work completed in this thesis was to find ways to improve 4D imaging using a gantry mounted 2D kV imaging system. Specifically, the goals were to investigate methods for minimizing imaging dose and scan time while achieving consistent, controllable, high quality 4D images.</p><p>First, we introduced four-dimensional digital tomosynthesis (4D DTS) and characterized its potential for 3D motion analysis using a motion phantom. The motion phantom was programmed to exhibit motion profiles with various known amplitudes in all three dimensions and scanned using a 2D kV imaging system mounted on a linear accelerator. Two arcs of projection data centered about the anterior-posterior and lateral axes were used to reconstruct phase resolved DTS coronal and sagittal images. Respiratory signals were obtained by analyzing projection data, and these signals were used to derive phases for each of the projection images. Projection images were sorted according to phase, and DTS phase images were reconstructed for each phase bin. 4D DTS target location accuracies for peak inhalation and peak exhalation in all three dimensions were limited only by the 0.5 mm pixel resolution for all DTS scan angles. The average localization errors for all phases of an assymetric motion profile with a 2 cm peak-to-peak amplitude were 0.68, 0.67 and 1.85 mm for 60 <super> o <super/> 4D DTS, 360<super> o <super/> CBCT and 4DCT, respectively. Motion artifacts for 4D DTS were found to be substantially less than those seen in 4DCT, which is the current clinical standard in 4D imaging. </p><p>We then developed a comprehensive framework for relating patient respiratory parameters with acquisition and reconstruction parameters for slow gantry rotation 4D DTS and 4D CBCT imaging. This framework was validated and optimized with phantom and lung patient studies. The framework facilitates calculation of optimal frame rates and gantry rotation speeds based on patient specific respiratory parameters and required temporal resolution (task dependent). We also conducted lung patient studies to investigate required scan angles for 4D DTS and achievable dose and scan times for 4D DTS and 4D CBCT using the optimized framework. This explicit and comprehensive framework of relationships allowed us to demonstrate that under-sampling artifacts can be controlled, and 4D CBCT images can be acquired using lower doses than previously reported. We reconstructed 4D CBCT images of three patients with accumulated doses of 4.8 to 5.7 cGy. These doses are three times less than the doses used for the only previously reported 4D CBCT investigation that did not report images characterized by severe under-sampling artifacts. </p><p>We found that scan times for 200<super> o <super/> 4D CBCT imaging using acquisition sequences optimized for reduction of imaging dose and under-sampling artifacts were necessarily between 4 and 7 minutes (depending on patient respiration). The results from lung patient studies concluded that scan times could be reduced using 4D DTS. Patient 4D DTS studies demonstrated that tumor visibility for the lung patients we studied could be achieved using 30<super> o <super/> scan angles for coronal views. Scan times for those cases were between 41 and 50 seconds. Additional dose reductions were also demonstrated. Image doses were between 1.56 and 2.13 cGy. These doses are well below doses for standard CBCT scans. The techniques developed and reported in this thesis demonstrate how respiratory motion can be imaged in the radiotherapy treatment room using clinically feasible imaging doses and scan times.</p> / Dissertation

A study was done at Steve Biko Academic hospital to determine the influence that respiratory gating will have on target volumes used in radiotherapy treatment planning. The primary objective was to compare target volumes of respiratory gated scans to ungated scans and to determine whether it will be meaningful to permanently implement a 4D respiratory gating system on CT scanners in the South African public health sector and to use these images for target volume delineation in radiotherapy planning. The study consisted of three sections. In the first section, 4D respiratory gated CT images were obtained and delineated with 4D software. The full-inspiration and full-expiration phases of the gated scans were then fused to obtain ungated images which were also delineated. The gross tumor volumes (GTVs) of the gated phases were compared to the ungated GTVs, and found that on average the volumes decreased by 14.63% with a standard deviation of 7.96% when gating was applied. Yet another aim was to determine the influence that 4D imaging will have on radiotherapy treatment planning. One of the 4D study sets was imported to the XIO treatment planning system where IMRT treatment plans were created on both the gated and ungated scans. The plans conformed to the treatment aims and restrictions when clinical parameters such as DVHs were used to evaluate it. The planned target volume coverage differed by less than 1% between the gated and the ungated plans, but significant dose reductions to the OARs of up to 32.65% to the contralateral lung were recorded on the gated plan. In the second section of this study, respiratory gated CT scans were simulated by applying the breath-hold technique to lung cancer patients. The technique was applied during full-inspiration which fundamentally represents the maximum peak of the sinusoidal respiratory waveform. An ungated scan was also acquired during normal respiration. The clinical target volumes (CTVs) were identified on both scans by three oncologists and the average CTVs were compared. It was found that the CTVs decreased significantly by an average of 14.33%. Palliative patients receive parallel opposing field therapy which is planned from 2D films. It is very unlikely that these opposing field sizes will differ when gating is applied. It was therefore concluded that only radical lung patients, which was estimated to be a mere 0.03% of the total radiation therapy patient population, will benefit by implementing respiratory gating or any motion-reduction technique. For the third section of the study, respiratory gated PET scans were acquired on a PET/CT scanner to evaluate external, non-technical parameters that will influence respiratory gating. The results indicated that time and patient participation were not limiting factors. The biggest concerns however were the effectiveness of the gating system, software limitations and the gated results. These problems might be minimized with thorough training on the system. All three sections as well as the financial implications were considered to conclude that it will not be meaningful to implement 4D respiratory gating techniques in the South African public health sector Copyright / Dissertation (MSc)--University of Pretoria, 2013. / Medical Oncology / unrestricted

No description available.

<p>Multiphase flow dynamics are integral to many propulsion, sprays, energetics, and industrial processes. Practical systems, especially in combustion, typically involve multidimensional spatial structures and complex and coupled physics interactions. At some operating conditions, flow mixing, combustion chemical reactions, and flow residence time scales are relatively similar and therefore coupled (i.e., each affects the other). For example, the combustion and atomization of liquid fuel govern the performance of combustors. In addition to spray-air interactions, injection strategies may rely on spray-wall interactions to achieve improved mixing and performance. Understanding and predicting these flows requires advanced experimental diagnostics that provide information on local state variables with high spatiotemporal resolution. However, multiphase flow dynamics integral to these combustion systems may not be fully resolved with conventional one or two-dimensional diagnostics. Tomographic reconstructions yield 3D spatial information and may provide high-fidelity data to fill the technology gap. Performing these 3D diagnostics with adequate time-resolution is necessary to capture the full dynamics of high-speed flows. This work focuses on developing, applying, and evaluating non-intrusive 4D (x,y,z,t) volumetric imaging in challenging combustion environments. Each optical diagnostic approach probes a different phase of combustion experiments in a non-instructive manner. For example, Schlieren imaging visualizes the index of refraction gradients corresponding to density changes in the gas phase. This work uses various optical approaches (e.g., scattering, Schlieren, or fluorescence) with 4D imaging to provide quantitative measurements of different combustion phenomena. Parallel ray-tracing simulations are utilized to guide diagnostic development and quantify measurement capabilities. This work presents significant high-speed diagnostic improvements for combustion applications relevant to defense, energy generation, and propulsion.</p>

<p>A bench-top dual cone-beam computed tomography (CBCT) system was developed consisting of two orthogonally placed 40x30 cm<super>2</super> flat-panel detectors and two conventional X-ray tubes with two individual high-voltage generators sharing the same rotational axis. The X-ray source to detector distance is 150 cm and X-ray source to rotational axis distance is 100 cm for both subsystems. The objects are scanned through 200° of rotation. The dual CBCT (DCBCT) system utilized 110° of projection data from one detector and 90° from the other while the two individual single CBCTs utilized 200° data from each detector. The system performance was characterized in terms of uniformity, contrast, spatial resolution, noise power spectrum and CT number linearity. The uniformity, within the axial slice and along the longitudinal direction, and noise power spectrum were assessed by scanning a water bucket; the contrast and CT number linearity were measured using the Catphan phantom; and the spatial resolution was evaluated using a tungsten wire phantom. A skull phantom and a ham were also scanned to provide qualitative evaluation of high- and low-contrast resolution. Each measurement was compared between dual and single CBCT systems.</p><p>Compared with single CBCT, the DCBCT presented: 1) a decrease in uniformity by 1.9% in axial view and 1.1% in the longitudinal view, as averaged for four energies (80, 100, 125 and 150 kVp); 2) comparable or slightly better contrast to noise ratio (CNR) for low-contrast objects and comparable contrast for high-contrast objects; 3) comparable spatial resolution; 4) comparable CT number linearity with R<super>2</super> &#8805; 0.99 for all four tested energies; 5) lower noise power spectrum in magnitude. DCBCT images of the skull phantom and the ham demonstrated both high-contrast resolution and good soft-tissue contrast.</p><p>One of the major challenges for clinical implementation of four-dimensional (4D) CBCT is the long scan time. To investigate the 4D imaging capabilities of the DCBCT system, motion phantom studies were conducted to validate the efficiency by comparing 4D images generated from 4D-DCBCT and 4D-CBCT. First, a simple sinusoidal profile was used to confirm the scan time reduction. Next, both irregular sinusoidal and patient-derived profiles were used to investigate the advantage of temporally correlated orthogonal projections due to a reduced scan time. Normalized mutual information (NMI) between 4D-DCBCT and 4D-CBCT was used for quantitative evaluation.</p><p>For the simple sinusoidal profile, the average NMI for ten phases between two single 4D-CBCTs was 0.336, indicating the maximum NMI that can be achieved for this study. The average NMIs between 4D-DCBCT and each single 4D-CBCT were 0.331 and 0.320. For both irregular sinusoidal and patient-derived profiles, 4D-DCBCT generated phase images with less motion blurring when compared with single 4D-CBCT.</p><p>For dual kV energy imaging, we acquired 80kVp projections and 150 kVp projections, with an additional 0.8 mm tin filtration. The virtual monochromatic (VM) technique was implemented, by first decomposing these projections into acrylic and aluminum basis material projections to synthesize VM projections, which were then used to reconstruct VM CBCTs. The effect of the VM CBCT on metal artifact reduction was evaluated with an in-house titanium-BB phantom. The optimal VM energy to maximize CNR for iodine contrast and minimize beam hardening in VM CBCT was determined using a water phantom containing two iodine concentrations. The linearly-mixed (LM) technique was implemented by linearly combining the low- (80kVp) and high-energy (150kVp) CBCTs. The dose partitioning between low- and high-energy CBCTs was varied (20%, 40%, 60% and 80% for low-energy) while keeping total dose approximately equal to single-energy CBCTs, measured using an ion chamber. Noise levels and CNRs for four tissue types were investigated for dual-energy LM CBCTs in comparison with single-energy CBCTs at 80, 100, 125 and 150kVp.</p><p>The VM technique showed a substantial reduction of metal artifacts at 100 keV with a 40% reduction in the background standard deviation compared with a 125 kVp single-energy scan of equal dose. The VM energy to maximize CNR for both iodine concentrations and minimize beam hardening in the metal-free object was 50 keV and 60 keV, respectively. The difference in average noise levels measured in the phantom background was 1.2% for dual-energy LM CBCTs and equivalent-dose single-energy CBCTs. CNR values in the LM CBCTs of any dose partitioning were better than those of 150 kVp single-energy CBCTs. The average CNRs for four tissue types with 80% dose fraction at low-energy showed 9.0% and 4.1% improvement relative to 100 kVp and 125 kVp single-energy CBCTs, respectively. CNRs for low contrast objects improved as dose partitioning was more heavily weighted towards low-energy (80kVp) for LM CBCTs.</p><p>For application of the dual-energy technique in the kilovoltage (kV) and megavoltage (MV) range, we acquired both MV projections (from gantry angle of 0° to 100°) and kV projections (90° to 200°) with the current orthogonal kV/MV imaging hardware equipped in modern linear accelerators, as gantry rotated a total of 110°. A selected range of overlap projections between 90° to 100° were then decomposed into two material projections using experimentally determined parameters from orthogonally stacked aluminum and acrylic step-wedges. Given attenuation coefficients of aluminum and acrylic at a predetermined energy, one set of VM projections could be synthesized from two corresponding sets of decomposed projections. Two linear functions were generated using projection information at overlap angles to convert kV and MV projections at non-overlap angles to approximate VM projections for CBCT reconstruction. The CNRs were calculated for different inserts in VM CBCTs of a CatPhan phantom with various selected energies and compared with those in kV and MV CBCTs. The effect of overlap projection number on CNR was evaluated. Additionally, the effect of beam orientation was studied by scanning the CatPhan sandwiched with two 5 cm solid-water phantoms on both lateral sides and an electronic density phantom with two metal bolt inserts.</p><p>Proper selection of VM energy (30keV and 40keV for low-density polyethylene (LDPE), polymethylpentene (PMP), 2MeV for Delrin) provided comparable or even better CNR results as compared with kV or MV CBCT. An increased number of overlap between kV and MV projections demonstrated only marginal improvements of CNR for different inserts (with the exception of LDPE) and therefore one projection overlap was found to be sufficient for the CatPhan study. It was also evident that the optimal CBCT image quality was achieved when MV beams penetrated through the heavy attenuation direction of the object. </p><p>In conclusion, the performance of a bench-top DCBCT imaging system has been characterized and is comparable to that of a single CBCT. The 4D-DCBCT provides an efficient 4D imaging technique for motion management. The scan time is reduced by approximately a factor of two. The temporally correlated orthogonal projections improved the image blur across 4D phase images. Dual-energy CBCT imaging techniques were implemented to synthesize VM CBCT and LM CBCTs. VM CBCT was effective at achieving metal artifact reduction. Depending on the dose-partitioning scheme, LM CBCT demonstrated the potential to improve CNR for low contrast objects compared with single-energy CBCT acquired with equivalent dose. A novel technique was developed to generate VM CBCTs from kV/MV projections. This technique has the potential to improve CNR at selected VM energies and to suppress artifacts at appropriate beam orientations.</p> / Dissertation

Made available in DSpace on 2016-12-12T20:15:51Z (GMT). No. of bitstreams: 1 Anderson Hoff.pdf: 11193047 bytes, checksum: f07cba24b1a4da1b53270bac747a0252 (MD5) Previous issue date: 2014-02-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Estruturas de bifurcação delimitam regiões periódicas imersas em áreas de caos em planos de parâmetros de sistemas dinâmicos. Neste trabalho são estudadas as estruturas de bifurcação de sistemas dinâmicos contínuos quadridimensionais, um circuito de Chua e um acoplamento de dois osciladores de FitzHugh-Nagumo. Os resultados numéricos foram obtidos através do cálculo dos expoentes de Lyapunov, através de integração numérica dos sistemas, e das curvas de bifurcação, por continuação numérica através do MatCont. Investigou-se as bifurcações que formam o endoesqueleto de camarões em planos de parâmetros no circuito de Chua, além de estruturas espirais, caos transiente e bacias de atração caóticas e periódicas. Análise semelhante foi realizada no acoplamento de dois osciladores de FitzHugh-Nagumo, identificando estruturas periódicas imersas em regiões caóticas, estruturas de línguas de Arnold imersas em regiões de comportamento quase-periódico, com períodos organizados e conectadas com regiões periódicas, e a sensibilidade do sistema às condições iniciais.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18139号 / 医博第3859号 / 新制||医||1002(附属図書館) / 30997 / 京都大学大学院医学研究科医学専攻 / (主査)教授 武藤 学, 教授 武田 俊一, 教授 富樫 かおり / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Nesta tese, buscou-se avaliar se a tomografia computadorizada de duplaenergia pós-contraste (TCDE) é capaz de detectar diferenças regionais da perfusão pulmonar em um modelo animal suíno incluindo variações de decúbito, lesão alveolar e oclusão da artéria pulmonar com balão, comparando estes resultados com os obtidos pela perfusão de primeira passagem com a tomografia computadorizada dinâmica (TCD). Dez suínos landrace foram divididos em Grupos A (N = 5, controle) e B (N = 5). Animais do Grupo B foram submetidos ao protocolo de lesão alveolar induzida por ventilação mecânica (LPIV). O volume sanguíneo perfundido e o fluxo sanguíneo pulmonar foram, respectivamente, estimados pela TCDE (%VSPTCDE) e pela TCD (FSPTCD), em diversas condições experimentais: posição supina versus prona, presença versus ausência de LPIV, presença ou ausência de oclusão da artéria pulmonar. A correlação entre %VSPTCDE e FSPTCD foi moderada (R = 0,60) com ampla variabilidade (intervalo 0,35-0,91) entre animais. %VSPTCDE e FSPTCD demonstraram padrões similares de heterogeneidade da perfusão pulmonar nas diferentes condições experimentais. Entretanto, reduções do %VSPTCDE causadas pela oclusão com balão foram em média -29,32 %, enquanto reduções do FSPTCD foram em média -86,78 % (p < 0,001). Estimativas quantitativas do VSPTCDE tiveram um erro médio de +4.3 ml/100g em comparação com o FSPTCD, com limites de concordância de 95 % entre -16,6 ml/100g e 25,1 ml/100g. A TCDE póscontraste é capaz de prover estimativas semiquantitativas que refletem a heterogeneidade regional da perfusão pulmonar causada por mudanças de decúbito, lesão alveolar e oclusão da artéria pulmonar com balão, apresentando moderada correlação com a perfusão de primeira passagem pela TCD / We aimed to evaluate whether contrast-enhanced dual-energy CT (DECT) detects regional pulmonary perfusion changes in a swine model of acute lung injury, with variations in decubitus and transient occlusion of the pulmonary artery, comparing these results with those obtained with dynamic CT perfusion (DynCT). Ten landrace swine were assigned to Groups A (N = 5, control) and B (N = 5). Group B was subjected to ventilator-induced lung injury (VILI). Perfused blood volume and pulmonary blood flow were quantified by DECT (PBVDECT) and DynCT (PBFDynCT), respectively, under different settings: supine versus prone, and with/without balloon occlusion of a pulmonary artery (PA) branch. Correlation of regional PBVDECT versus PBFDynCT was moderate (R = 0.60) with high variability (range 0.35-0.91) among the animals. Regional pulmonary perfusion changes assessed by %PBVDECT agreed with PBFDynCT in response to decubitus changes, lung injury and balloon occlusion in the multivariate analysis. However, reductions in %PBVDECT caused by balloon occlusion were in average -29.32 %, whereas reductions in PBFDynCT were in average -86.78 % (p < 0.001). Quantitative estimates of PBVDECT had a mean bias of +4.3 ml/100g in comparison with PBVDynCT, with 95 % confidence intervals between -16.6 ml/100g and 25.1 ml/100g. Semiquantitative contrastenhanced DECT reflects regional changes in perfusion caused decubitus changes, acute lung injury, and balloon occlusion of the PA, with moderate correlation in comparison with DynCT