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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
211

A "Label-Free" Method for the Determination of Polyethylene-Glycol Functionalization Efficiency on Gold Monolayer Protected Clusters

Bell, Charleson Sherard 15 December 2009 (has links)
Most bionanotechnology-based agents require careful control of surface properties to improve vascular circulation time, control delivery characteristics and provide biocompatibility, especially when used for diagnostics or therapy. The number and type of protective and targeting ligands modulate the interactions of such bionanoparticles with living systems. A method for quantifying the number of ligands associated with the surface of a bionanoparticle would be a useful tool. Here, label-free methods of conjugate quantification are described. These approaches circumvent the potentially disadvantageous surface packing defects introduced by labels used in previous methods. Conjugated PEG-S ligands were quantified using 1H nuclear magnetic resonance (NMR) spectroscopy and inductively coupled plasma mass spectroscopy (ICP-AES). Normalized NMR and ICP-AES enumeration of conjugated ligands aligned with predictions based on a previously determined molecular footprint. The ligand packing density significantly decreases as available particulate surface area decreases for particle sizes from 100 nm to 5 nm. Steric hindrance and packing inefficiencies are presumed to decrease ligand binding per unit surface area for small particle diameters relative to larger particles. In addition, the packing density begins to become more constant for sizes ranging from 100 nm to 250 nm. PEG packing in this system is most efficient on particle diameters of approximately the erected length of the conjugated polymer. These results imply that the potential for maximizing bionanoparticulate effectiveness lies in the careful design and knowledge of the loading and packing profile of the protecting or targeting ligands that will be loaded on the desired particulate platform.
212

Investigation of the Effect of Tissue Water Dynamics on Compartmental MRI Measurements using Contrast Enhanced Relaxometry and SPECT

Skinner, Jack Thomas 11 April 2012 (has links)
Magnetic resonance imaging (MRI) provides methods for characterizing tissue micro-structure using relaxation-based measurements with and without the use of contrast agents (CA). Two techniques, dynamic contrast enhanced MRI (DCE-MRI) and multiple spin-echo (MSE) imaging, often employ two-pool models to obtain estimates of tissue compartment sizes. These estimates can be biased, however, by tissue water dynamics. Alternate strategies, such as single photon emission computed tomography (SPECT) imaging, can provide measures of tissue compartment size unbiased by water exchange. In this work, DCE-MRI measurements in rat brain tumor were compared to a dual-isotope SPECT method to assess the accuracy of estimates of the extracellular volume fraction extracted from common pharmacokinetic models. In addition, quantitative SPECT was used to validate a novel contrast enhanced MSE method, in injured rat skeletal muscle, for estimating in vivo inter-compartmental water exchange. In an effort to translate similar MSE techniques to human imaging, an accelerated method for accurate compartmental relaxometry was also evaluated.
213

OPTICAL IMAGING OF METABOLISM IN HER2 OVEREXPRESSING CELLS

Walsh, Alexandra Jule 09 April 2012 (has links)
The optical redox ratio (fluorescence intensity of NADH divided by that of FAD), was acquired for a panel of breast cancer cell lines to investigate how overexpression of human epidermal growth factor receptor 2 (HER2) affects tumor cell metabolism, and how tumor metabolism may be altered in response to clinically used HER2-targeted therapies. Confocal fluorescence microscopy was used to acquire NADH and FAD auto-fluorescent images. The optical redox ratio was highest in cells overexpressing HER2 and lowest in triple negative breast cancer (TNBC) cells, which lack HER2, progesterone receptor, and estrogen receptor (ER). The redox ratio in ER-positive/HER2-negative cells was higher than what was seen in TNBC cells, but lower than that in HER2 overexpressing cells. Importantly, inhibition of HER2 using trastuzumab significantly reduced the redox ratio in HER2 overexpressing cells. Furthermore, the combinatorial inhibition of HER2 and ER decreased the redox ratio in ER+/HER2+ breast cancer cells to a greater extent than inhibition of either receptor alone. Interestingly, trastuzumab had little impact upon the redox ratio in a cell line selected for acquired resistance to trastuzumab. Taken together, these data indicate that the optical redox ratio measures changes in tumor metabolism that reflect the oncogenic effects of HER2 activity within the cell, as well as the response of the cell to therapeutic inhibition of HER2. Therefore, optical redox imaging holds the promise of measuring response and resistance to receptor-targeted breast cancer therapies in real time, which could potentially impact clinical decisions and improve patient outcome.
214

Imaging of Osteolytic Breast Cancer Metastases with Computed Tomography, Positron Emission Tomography and Single Photon Emission Computed Tomography

Johnson, Lindsay Craig 12 April 2010 (has links)
Imaging protocols for detection of breast cancer metastases to bone in clinical imaging have long been standardized, but to date small animal imaging still uses a variety of imaging modalities and protocols. Although imaging with modalities such as computed tomography (CT), positron emission tomography (PET), and single photon emission computed tomography (SPECT) are commonly performed, there has been little investigation into the quantitative capability of each modality. The first part of this project investigated the ability to quantify bone volume changes using longitudinal CT scans of mice that were injected in the tibia with MDA-MB-231 cancer cells. CT images were acquired weekly for four weeks for both a treatment and a control group. Tibial volumes were calculated by applying a bone threshold to reconstructed images. Statistically significant differences were found between the untreated lesion and control limb volumes (p<0.0001) and between the treated and untreated lesion limb volumes (p<0.0001). For the second part of this project, a comparison of PET and SPECT for bone imaging using fluoride-18 and technetium-99m methylene diphosphonate, respectively, was performed based on protocols that delivered the same estimated absorbed radiation dose to bone. A same-day imaging protocol with PET, SPECT, and microCT was developed and implemented on three mice that had previously received a cardiac-injection of cancer cells. Visual inspection and quantitative analysis showed mixed results, implying further investigation is necessary to determine which modality is better suited for this application of bone imaging.
215

A NOVEL OPTICAL APPROACH TO THE INTRAOPERATIVE DETECTION OF PARATHYROID GLANDS

Paras, Constantine A 16 December 2009 (has links)
A major challenge in endocrine surgery is the intraoperative identification of parathyroids during both thyroid and parathyroid surgery. Current localization techniques are mostly preoperative and are imprecise. Optical spectroscopy is fast and sensitive and has been used in many in vivo applications. Here, near-infrared (NIR) fluorescence is used to identify parathyroid glands during thyroid and parathyroidectomies. We investigated whether parathyroid tissue had unique optical signals that could be used to identify the parathyroid glands and differentiate them from other tissues in the neck intra-operatively. Fluorescence measurements were obtained from patients undergoing endocrine surgery at Vanderbilt University Medical Center. The intensity of the parathyroid signal was compared to the fluorescence of the surrounding tissue including the thyroid gland. In each case, the parathyroid had markedly higher levels of fluorescence. These results indicate that NIR fluorescence is potentially an excellent tool to locate parathyroid tissue during surgery.
216

DEVELOPMENT OF COMBINED RAMAN SPECTROSCOPY - OPTICAL COHERENCE TOMOGRAPHY FOR THE DETECTION OF SKIN CANCER

Patil, Chetan Appasaheb 23 December 2009 (has links)
Skin cancer is the most common cancer in the United States, with an incidence rate that continues to rise. Fortunately, it can be highly curable if detected at an early stage. Best clinical practices require physicians to screen large areas of skin, identify suspicious lesions, perform biopsies, and await the results for disease diagnosis. This paradigm is not ideal. Identification of questionable lesions can be subjective, biopsy is invasive and painful, and pathological analysis is time consuming and costly. The potential of a variety of novel optical techniques to perform rapid, non-invasive optical biopsy has been widely touted; however these methods suffer unique limitations. Raman spectroscopy (RS) can classify lesions with high accuracy due to its inherent biochemical sensitivity; however it is unable to relate microstructural features of disease. Conversely, optical coherence tomography (OCT) can image tissue microstructure but lacks molecular specificity. The two methods are ideally complimentary and thus well-suited for combination into a single instrument to meet the challenge optical biopsy presents. The primary objective of this dissertation is to develop the novel technique of combined RS-OCT for characterization skin cancers. A pilot study that identifies the capabilities and limitations of RS for skin cancer diagnosis was performed in the first aim, and motivates the development of combined RS-OCT. The second aim demonstrates the feasibility and benefit of combined RS-OCT in a benchtop instrument with integrated RS and OCT sampling optics. The third aim is the development of a second generation instrument which further integrates the systems at the detector level. The final aim reports the implementation of an instrument and probe capable of combined RS-OCT analysis of skin cancers in a clinical setting. The results of this dissertation represent a significant step towards the ultimate goal of optical biopsy.
217

Intra-operative Registration Methods for Image-Guided Kidney Surgery

Ong, Rowena E 21 April 2012 (has links)
In this work, I examined, developed, and validated methods for intra-operative registration in minimally invasive kidney surgery. One of these methods uses a conoscopic laser that can be inserted through a small trocar port to scan the kidney and obtain a surface point cloud. To enable intra-operative feature tracking, a novel method for texture-mapping the conoscopic surface was developed using laparoscopic video. The feasibility and accuracy of this texture-mapping method was evaluated. In addition, a registration method using features tracked from the textured-mapped conoscopic surfaces was investigated for use in-vivo, under laparoscopic conditions in swine. The feasibility and accuracy of the registration method was investigated and shown to be promising. Finally, to evaluate the need for non-rigid deformation correction in an image guidance system for the kidney, a preliminary study of non-rigid deformation in the kidney was performed. In this study, ex-vivo porcine kidneys were perfused, the renal vessels clamped, and an incision was made to simulate surgical conditions. The resulting deformation was measured, and the fiducial-tracked displacements were interpolated using a spline. The accuracy of this method was assessed, and the results show this method could be used with tracked features from intra-operative conoscopic scans to correct for non-rigid deformation.
218

Evaluation of atlas-based brain shift model for improved adaptation to intraoperative neurosurgical conditions

Chen, Ishita 04 May 2012 (has links)
Image guidance utilizes a rigid registration between the preoperative images and physical space of the operating room and it is now the standard of care in neurosurgical procedures. The fidelity of the image guidance system is known to be compromised by the extensively studied phenomenon of brain shift. A considerable body of work in literature has focused on solving this problem either through intraoperative imaging or by updating preoperative images with mathematical models. The factors that affect the magnitude and the direction of tissue deformation cannot be predicted to exact precision before the procedure and are often difficult to measure during the procedure. In previous literature, to account for this uncertainty, a statistical atlas-based method was used to capture the range of possible solutions. This work was validated using postoperative magnetic resonance (MR) data. Postoperative MR images are typically acquired after a lapse of 24 hours of surgery, during which period a shift recovery is known to occur. As a result, the postoperative measurements are typically smaller than what would be observed intraoperatively. Moreover the surgical environment is quite dynamic due to active tissue resection and retraction, which affect the observed displacements in the region of the craniotomy. The goal of this work was to systematically study the differences between the pre- and post-operative MR deformation and preoperative MR and intraoperative laser range scan deformation and devise strategies to better adapt the atlas-based model for intraoperative conditions. Strategies for improving the subsurface accuracy by accounting for the dural septa were studied. In order to make the atlas-based method feasible for intraoperative implementation, methods for automation of brain and dural septa segmentation were developed. Sensitivity analysis was performed to determine the impact of atlas resolution on accuracy. Lastly, preliminary studies for integration of intraoperative forces of retraction and resection into the atlas-based model were conducted. The results of these studies provide important conclusions to advance the goal of implementation of an efficient and cost-effective brain shift correction strategy for the neurosurgical image guidance.
219

Development of a Simultaneous Cryo-Anchoring and Radiofrequency Ablation Catheter for Percutaneous Treatment of Mitral Valve Prolapse

Boronyak, Steven Michael 05 April 2012 (has links)
Mitral valve prolapse is one subtype of mitral valve disease and is characterized by enlarged leaflets that are often thickened and have disrupted collagen architecture. The increased surface area of leaflets with mitral valve prolapse leads to mitral regurgitation, and there is need for percutaneous treatment options that avoid open-chest surgery. Radiofrequency ablation is one potential therapy in which resistive heating can be used to reduce leaflet size via collagen contracture. One challenge of using radiofrequency ablation to percutaneously treat mitral valve prolapse is maintaining contact between the radiofrequency ablation catheter tip and a functioning mitral valve leaflet. To meet this challenge, a radiofrequency ablation catheter was developed with a cryogenic anchor for attachment to leaflets. The effectiveness of the dual-energy catheter was demonstrated in vitro by examining changes in leaflet biaxial compliance, thermal distribution with infrared imaging, and cryogenic anchor strength. The results indicate that a catheter having combined radiofrequency ablation and cryo-anchoring provides a novel percutaneous treatment strategy for mitral valve prolapse.
220

Posterior Hepatic Detection Using Ultrasound for Deformation Correction in Image Guided Liver Surgery

Ondrake, Janet Elizabeth 06 August 2012 (has links)
This project involves the use of ultrasound imaging as a method to acquire posterior surface information intraoperatively for the use in deformation correction for image guided liver surgery. In this thesis, the subsurface effects of deformation correction were explored using a more realistic phantom model to replicated liver deformation that occurs during surgery. The use of intraoperative ultrasound as a possible modality for surface acquisition was investigated using simulated surfaces from computational tomography volumes and segmented tracked ultrasound images. The incorporation of a partial posterior surface from ultrasound showed a significant improvement in guidance capability, reducing the mean target registration error by 4.1 mm in the operating region of interest. Despite the remaining obstacles, the results in this work demonstrated the potential of using ultrasound, a widely accepted tool, as a practical posterior surface detection method in deformation correction in image guided liver surgery.

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