Matching Items (20)
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- All Subjects: Biomedical Engineering
- Genre: Academic theses
- Creators: Kodibagkar, Vikram
Description
Image resolution limits the extent to which zooming enhances clarity, restricts the size digital photographs can be printed at, and, in the context of medical images, can prevent a diagnosis. Interpolation is the supplementing of known data with estimated values based on a function or model involving some or all of the known samples. The selection of the contributing data points and the specifics of how they are used to define the interpolated values influences how effectively the interpolation algorithm is able to estimate the underlying, continuous signal. The main contributions of this dissertation are three fold: 1) Reframing edge-directed interpolation of a single image as an intensity-based registration problem. 2) Providing an analytical framework for intensity-based registration using control grid constraints. 3) Quantitative assessment of the new, single-image enlargement algorithm based on analytical intensity-based registration. In addition to single image resizing, the new methods and analytical approaches were extended to address a wide range of applications including volumetric (multi-slice) image interpolation, video deinterlacing, motion detection, and atmospheric distortion correction. Overall, the new approaches generate results that more accurately reflect the underlying signals than less computationally demanding approaches and with lower processing requirements and fewer restrictions than methods with comparable accuracy.
ContributorsZwart, Christine M. (Author) / Frakes, David H (Thesis advisor) / Karam, Lina (Committee member) / Kodibagkar, Vikram (Committee member) / Spanias, Andreas (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2013
Description
Cancer is the second leading cause of death in the United States and novel methods of treating advanced malignancies are of high importance. Of these deaths, prostate cancer and breast cancer are the second most fatal carcinomas in men and women respectively, while pancreatic cancer is the fourth most fatal in both men and women. Developing new drugs for the treatment of cancer is both a slow and expensive process. It is estimated that it takes an average of 15 years and an expense of $800 million to bring a single new drug to the market. However, it is also estimated that nearly 40% of that cost could be avoided by finding alternative uses for drugs that have already been approved by the Food and Drug Administration (FDA). The research presented in this document describes the testing, identification, and mechanistic evaluation of novel methods for treating many human carcinomas using drugs previously approved by the FDA. A tissue culture plate-based screening of FDA approved drugs will identify compounds that can be used in combination with the protein TRAIL to induce apoptosis selectively in cancer cells. Identified leads will next be optimized using high-throughput microfluidic devices to determine the most effective treatment conditions. Finally, a rigorous mechanistic analysis will be conducted to understand how the FDA-approved drug mitoxantrone, sensitizes cancer cells to TRAIL-mediated apoptosis.
ContributorsTaylor, David (Author) / Rege, Kaushal (Thesis advisor) / Jayaraman, Arul (Committee member) / Nielsen, David (Committee member) / Kodibagkar, Vikram (Committee member) / Dai, Lenore (Committee member) / Arizona State University (Publisher)
Created2013
Description
Magnetic Resonance Imaging using spiral trajectories has many advantages in speed, efficiency in data-acquistion and robustness to motion and flow related artifacts. The increase in sampling speed, however, requires high performance of the gradient system. Hardware inaccuracies from system delays and eddy currents can cause spatial and temporal distortions in the encoding gradient waveforms. This causes sampling discrepancies between the actual and the ideal k-space trajectory. Reconstruction assuming an ideal trajectory can result in shading and blurring artifacts in spiral images. Current methods to estimate such hardware errors require many modifications to the pulse sequence, phantom measurements or specialized hardware. This work presents a new method to estimate time-varying system delays for spiral-based trajectories. It requires a minor modification of a conventional stack-of-spirals sequence and analyzes data collected on three orthogonal cylinders. The method is fast, robust to off-resonance effects, requires no phantom measurements or specialized hardware and estimate variable system delays for the three gradient channels over the data-sampling period. The initial results are presented for acquired phantom and in-vivo data, which show a substantial reduction in the artifacts and improvement in the image quality.
ContributorsBhavsar, Payal (Author) / Pipe, James G (Thesis advisor) / Frakes, David (Committee member) / Kodibagkar, Vikram (Committee member) / Arizona State University (Publisher)
Created2013
Description
Coronary computed tomography angiography (CTA) has a high negative predictive value for ruling out coronary artery disease with non-invasive evaluation of the coronary arteries. My work has attempted to provide metrics that could increase the positive predictive value of coronary CTA through the use of dual energy CTA imaging. After developing an algorithm for obtaining calcium scores from a CTA exam, a dual energy CTA exam was performed on patients at dose levels equivalent to levels for single energy CTA with a calcium scoring exam. Calcium Agatston scores obtained from the dual energy CTA exam were within ±11% of scores obtained with conventional calcium scoring exams. In the presence of highly attenuating coronary calcium plaques, the virtual non-calcium images obtained with dual energy CTA were able to successfully measure percent coronary stenosis within 5% of known stenosis values, which is not possible with single energy CTA images due to the presence of the calcium blooming artifact. After fabricating an anthropomorphic beating heart phantom with coronary plaques, characterization of soft plaque vulnerability to rupture or erosion was demonstrated with measurements of the distance from soft plaque to aortic ostium, percent stenosis, and percent lipid volume in soft plaque. A classification model was developed, with training data from the beating heart phantom and plaques, which utilized support vector machines to classify coronary soft plaque pixels as lipid or fibrous. Lipid versus fibrous classification with single energy CTA images exhibited a 17% error while dual energy CTA images in the classification model developed here only exhibited a 4% error. Combining the calcium blooming correction and the percent lipid volume methods developed in this work will provide physicians with metrics for increasing the positive predictive value of coronary CTA as well as expanding the use of coronary CTA to patients with highly attenuating calcium plaques.
ContributorsBoltz, Thomas (Author) / Frakes, David (Thesis advisor) / Towe, Bruce (Committee member) / Kodibagkar, Vikram (Committee member) / Pavlicek, William (Committee member) / Bouman, Charles (Committee member) / Arizona State University (Publisher)
Created2013
Description
Sensitivity is a fundamental challenge for in vivo molecular magnetic resonance imaging (MRI). Here, I improve the sensitivity of metal nanoparticle contrast agents by strategically incorporating pure and doped metal oxides in the nanoparticle core, forming a soluble, monodisperse, contrast agent with adjustable T2 or T1 relaxivity (r2 or r1). I first developed a simplified technique to incorporate iron oxides in apoferritin to form "magnetoferritin" for nM-level detection with T2- and T2* weighting. I then explored whether the crystal could be chemically modified to form a particle with high r1. I first adsorbed Mn2+ ions to metal binding sites in the apoferritin pores. The strategic placement of metal ions near sites of water exchange and within the crystal oxide enhance r1, suggesting a mechanism for increasing relaxivity in porous nanoparticle agents. However, the Mn2+ addition was only possible when the particle was simultaneously filled with an iron oxide, resulting in a particle with a high r1 but also a high r2 and making them undetectable with conventional T1-weighting techniques. To solve this problem and decrease the particle r2 for more sensitive detection, I chemically doped the nanoparticles with tungsten to form a disordered W-Fe oxide composite in the apoferritin core. This configuration formed a particle with a r1 of 4,870mM-1s-1 and r2 of 9,076mM-1s-1. These relaxivities allowed the detection of concentrations ranging from 20nM - 400nM in vivo, both passively injected and targeted to the kidney glomerulus. I further developed an MRI acquisition technique to distinguish particles based on r2/r1, and show that three nanoparticles of similar size can be distinguished in vitro and in vivo with MRI. This work forms the basis for a new, highly flexible inorganic approach to design nanoparticle contrast agents for molecular MRI.
ContributorsClavijo Jordan, Maria Veronica (Author) / Bennett, Kevin M (Thesis advisor) / Kodibagkar, Vikram (Committee member) / Sherry, A Dean (Committee member) / Wang, Xiao (Committee member) / Yarger, Jeffery (Committee member) / Arizona State University (Publisher)
Created2012
Description
Ionizing radiation, such as gamma rays and X-rays, are becoming more widely used. These high-energy forms of electromagnetic radiation are present in nuclear energy, astrophysics, and the medical field. As more and more people have the opportunity to be exposed to ionizing radiation, the necessity for coming up with simple and quick methods of radiation detection is increasing. In this work, two systems were explored for their ability to simply detect ionizing radiation. Gold nanoparticles were formed via radiolysis of water in the presence of Elastin-like polypeptides (ELPs) and also in the presence of cationic polymers. Gold nanoparticle formation is an indicator of the presence of radiation. The system with ELP was split into two subsystems: those samples including isopropyl alcohol (IPA) and acetone, and those without IPA and acetone. The samples were exposed to certain radiation doses and gold nanoparticles were formed. Gold nanoparticle formation was deemed to have occurred when the sample changed color from light yellow to a red or purple color. Nanoparticle formation was also checked by absorbance measurements. In the cationic polymer system, gold nanoparticles were also formed after exposing the experimental system to certain radiation doses. Unique to the polymer system was the ability of some of the cationic polymers to form gold nanoparticles without the samples being irradiated. Future work to be done on this project is further characterization of the gold nanoparticles formed by both systems.
ContributorsWalker, Candace (Author) / Rege, Kaushal (Thesis advisor) / Chang, John (Committee member) / Kodibagkar, Vikram (Committee member) / Potta, Thrimoorthy (Committee member) / Arizona State University (Publisher)
Created2012
Description
Allogeneic islet transplantation has the potential to reverse Type 1 Diabetes in patients. However, limitations such as chronic immunosuppression, islet donor numbers, and islet survival post-transplantation prevent the widespread application of allogeneic islet transplantation as the treatment of choice. Macroencapsulation devices have been widely used in allogeneic islet transplantation due to their capability to shield transplanted cells from the immune system as well as provide a supportive environment for cell viability, but macroencapsulation devices face oxygen transport challenges as their geometry increases from preclinical to clinical scales. The goal of this work is to generate complex 3D hydrogel macroencapsulation devices with sufficient oxygen transport to support encapsulated cell survival and generate these devices in a way that is accessible in the clinic as well as scaled manufacturing. A 3D-printed injection mold has been developed to generate hydrogel-based cell encapsulation devices with spiral geometries. The spiral geometry of the macroencapsulation device facilitates greater oxygen transport throughout the whole device resulting in improved islet function in vivo in a syngeneic rat model. A computational model of the oxygen concentration within macroencapsulation devices, validated by in vitro analysis, predicts that cells and islets maintain a greater viability and function in the spiral macroencapsulation device. To further validate the computational model, pO2 Reporter Composite Hydrogels (PORCH) are engineered to enable spatiotemporal measurement of oxygen tension within macroencapsulation devices using the Proton Imaging of Siloxanes to map Tissue Oxygenation Levels (PISTOL) magnetic resonance imaging approach. Overall, a macroencapsulation device geometry designed via computational modeling of device oxygen gradients and validated with magnetic resonance (MR) oximetry imaging enhances islet function and survival for islet transplantation.
ContributorsEmerson, Amy (Author) / Weaver, Jessica (Thesis advisor) / Kodibagkar, Vikram (Committee member) / Sadleir, Rosalind (Committee member) / Stabenfeldt, Sarah (Committee member) / Wang, Kuei-Chun (Committee member) / Arizona State University (Publisher)
Created2023
Description
Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, causing nearly 25% of deaths in the United States. Despite the efforts to create in vitro models for the study and treatment of CVDs, these are still limited in their recapitulation of the heart tissue. Thus, the engineering of accurate cardiac models is imperative to gain more understanding and improve the outcome of CVDs. This Ph.D. dissertation focuses on the development and characterization of isogenic cardiac organoids derived from human induced pluripotent stem cells (hiPSCs). Additionally, the integration of chemical and biological cues for enriching their microenvironment and promoting their maturation state and function were studied. First, hiPSC-derived cardiac cells were utilized for the fabrication of multicellular spherical microtissues, namely isogenic cardiac organoids. The cellular composition and culture time of the engineered tissues were optimized to induce cellular aggregation and the formation of cell-cell interactions. Also, ribbon-like gold nanoparticles, namely gold nanoribbons (AuNRs), were synthesized, characterized, and biofunctionalized for their integration into the isogenic cardiac organoids. In-depth biological evaluation of the organoids showed enhanced cardiac maturation markers. Furthermore, a supplement-free cell culture regime was designed and evaluated for fabricating isogenic cardiac organoids. Mechanistic, cellular, and molecular-level studies demonstrated that the presence of hiPSC-derived cardiac fibroblasts (hiPSC-CFs) significantly improves the morphology and gene expression profile of the organoids. Electrophysiological-relevant features of the organoids, such as conduction velocity (CV), were further investigated utilizing a microelectrode array (MEA) platform. It was shown that MEA offers a simple, yet powerful approach to assessing electrophysiological responses of the tissues, where a trend in decreased CV was found due to the presence of hiPSC-CFs. Overall, this dissertation has a broad impact casting light on the development strategy and biological mechanisms that govern the formation and function of isogenic cardiac organoids. Moreover, this study presents two unique approaches to promote maturation of stem cell-derived cardiac organoids: 1) through the integration of novel biofunctionalized nanomaterials, and 2) through a cell culture regime, leading to enhanced function of the organoids. The proposed micro-engineered organoids have broad applications as physiologically relevant tissues for drug discovery, CVDs modeling, and regenerative medicine.
ContributorsPatino, Alejandra (Author) / Nikkhah, Medhi (Thesis advisor) / Blain-Christen, Jennifer (Committee member) / Kodibagkar, Vikram (Committee member) / Vernon, Brent (Committee member) / Zhu, Wuqiang (Committee member) / Arizona State University (Publisher)
Created2023
Description
A direct Magnetic Resonance (MR)-based neural activity mapping technique with high spatial and temporal resolution may accelerate studies of brain functional organization.
The most widely used technique for brain functional imaging is functional Magnetic Resonance Image (fMRI). The spatial resolution of fMRI is high. However, fMRI signals are highly influenced by the vasculature in each voxel and can be affected by capillary orientation and vessel size. Functional MRI analysis may, therefore, produce misleading results when voxels are nearby large vessels. Another problem in fMRI is that hemodynamic responses are slower than the neuronal activity. Therefore, temporal resolution is limited in fMRI. Furthermore, the correlation between neural activity and the hemodynamic response is not fully understood. fMRI can only be considered an indirect method of functional brain imaging.
Another MR-based method of functional brain mapping is neuronal current magnetic resonance imaging (ncMRI), which has been studied over several years. However, the amplitude of these neuronal current signals is an order of magnitude smaller than the physiological noise. Works on ncMRI include simulation, phantom experiments, and studies in tissue including isolated ganglia, optic nerves, and human brains. However, ncMRI development has been hampered due to the extremely small signal amplitude, as well as the presence of confounding signals from hemodynamic changes and other physiological noise.
Magnetic Resonance Electrical Impedance Tomography (MREIT) methods could have the potential for the detection of neuronal activity. In this technique, small external currents are applied to a body during MR scans. This current flow produces a magnetic field as well as an electric field. The altered magnetic flux density along the main magnetic field direction caused by this current flow can be obtained from phase images. When there is neural activity, the conductivity of the neural cell membrane changes and the current paths around the neurons change consequently. Neural spiking activity during external current injection, therefore, causes differential phase accumulation in MR data. Statistical analysis methods can be used to identify neuronal-current-induced magnetic field changes.
The most widely used technique for brain functional imaging is functional Magnetic Resonance Image (fMRI). The spatial resolution of fMRI is high. However, fMRI signals are highly influenced by the vasculature in each voxel and can be affected by capillary orientation and vessel size. Functional MRI analysis may, therefore, produce misleading results when voxels are nearby large vessels. Another problem in fMRI is that hemodynamic responses are slower than the neuronal activity. Therefore, temporal resolution is limited in fMRI. Furthermore, the correlation between neural activity and the hemodynamic response is not fully understood. fMRI can only be considered an indirect method of functional brain imaging.
Another MR-based method of functional brain mapping is neuronal current magnetic resonance imaging (ncMRI), which has been studied over several years. However, the amplitude of these neuronal current signals is an order of magnitude smaller than the physiological noise. Works on ncMRI include simulation, phantom experiments, and studies in tissue including isolated ganglia, optic nerves, and human brains. However, ncMRI development has been hampered due to the extremely small signal amplitude, as well as the presence of confounding signals from hemodynamic changes and other physiological noise.
Magnetic Resonance Electrical Impedance Tomography (MREIT) methods could have the potential for the detection of neuronal activity. In this technique, small external currents are applied to a body during MR scans. This current flow produces a magnetic field as well as an electric field. The altered magnetic flux density along the main magnetic field direction caused by this current flow can be obtained from phase images. When there is neural activity, the conductivity of the neural cell membrane changes and the current paths around the neurons change consequently. Neural spiking activity during external current injection, therefore, causes differential phase accumulation in MR data. Statistical analysis methods can be used to identify neuronal-current-induced magnetic field changes.
ContributorsFu, Fanrui (Author) / Sadleir, Rosalind (Thesis advisor) / Kodibagkar, Vikram (Committee member) / Kleim, Jeffrey (Committee member) / Muthuswamy, Jitendran (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2019
Description
There is a critical need for creating an implantable microscale neural interface that can chronically monitor neural activity and oxygenation. These are key aspects for understating the development of impaired neural circuits and their functions. A technology with such capability would foster new insights in the studies of brain diseases and disorders. The propose is that MR-PISTOL (Proton imaging of Siloxane to Map Tissue Oxygenation Levels) imaging technique can be used for direct measurements of oxygen partial pressure at microelectrode-tissue interface. The strategy consists of coating microelectrodes with soft-silicone, a ultra-soft conductive PDMS (polydimethylsiloxane), as a carrier for liquid siloxanes MR-PISTOL contrast agents. This work presents a proof-of-concept of an injection molding technique for batch fabricate microelectrodes with such coating. Also, reports stability studies of soft-silicone loaded with liquid polydimethylsiloxane (PDMSO) in rodent brains. A batch of thirty coated carbon electrodes was achieved using candy molds. Coating uniformity was evaluated in twelve probes. They were randomly chosen and imaged with a custom image setup that allows 90o rotation of the probes. The total average coating thickness before and after rotation were 0.397 millimeters with standard deviation of 0.070 millimeters and 0.442 millimeters with standard deviation of 0.062 millimeters. Therefore, data confirms that this technique yields uniform coating. Stability of fabricated coated carbon electrodes unloaded (n= 3) and loaded with PDMSO (n= 3) was assessed. 3D X-ray imaging using Zeiss Xradia 520 machine was chosen for studying coatings mechanical stability in ex-vivo rat brain. Transmission electron microscopy (TEM) and scanning electron microscope (SEM) with an energy dispersive x-ray microanalysis (EDS) detector were used to investigate their chemical stability in in vivo mouse brain. Initial EDS analysis from TEM and SEM of acute (6 hours) and chronic (2 weeks) brain slices suggest that PDMSO does not leach into brain. More experiments should be done to confirm and endorse this finding. The mechanical study shows that coating loaded with PDMSO delaminated during insertion. This was not observed with electrodes used in the chemical stability studies. Further experiments need to be done to identify possible causes of mechanical failures.
Contributorsde Mesquita Teixeira, Livia (Author) / Muthuswamy, Jitendran (Thesis advisor, Committee member) / Kodibagkar, Vikram (Thesis advisor, Committee member) / Sridharan, Arati (Committee member) / Arizona State University (Publisher)
Created2018