Scholarship & Research
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Item Magnetic resonance imaging studies of forced and free convective heat transfer in packed beds and fluid columns(Montana State University - Bozeman, College of Engineering, 2021) Skuntz, Matthew Eric; Chairperson, Graduate Committee: Ryan Anderson; This is a manuscript style paper that includes co-authored chapters.Prediction of fluid flow and associated energy transport is an essential component in many engineering applications where analytical solutions are not possible. In these systems experimentation and numerical simulations are a necessary part of the design process. This work focuses on the experimental study of mass and energy transport in packed beds and pure fluids under forced and natural convection using nuclear magnetic resonance (NMR) imaging (MRI) techniques. It further evaluates the efficacy of commercial computational fluid dynamics (CFD) software to simulate these processes. The study of heat transfer via NMR has proven difficult historically, despite sensitivity of NMR parameters to temperature. Here, a novel experimental setup is pioneered, which enables the study of heat transfer in packed beds. The method employs fluorinated pore-filling fluid and hydrogen-rich core-shell packing particles. Hydrogen and fluorine are NMR-active chemicals that can be imaged with the same experimental equipment by adjusting the resonance frequency; providing means to image the two domains separately. Pore- fluid velocities and particle-wax melting are observed in the same packed bed, at sub-millimeter resolutions, presenting a more complete picture of the conditions in these hard-to-measure systems. In the presented studies, this methodology is demonstrated under forced convection and proven capable in identifying and correlating spatial variations in heat transfer to pore-fluid velocity. The technique is then employed to assess the accuracy of a CFD model in the commercial software package, STAR CCM+, using the melt to quantify energy absorbed by the bed. In natural convection studies of a pure fluid and packed bed in the Rayleigh-Bénard configuration, the axial circulation pattern is found to change with axial position in the long narrow cylinder, a result that is rarely discussed in literature. A CFD model is shown to match well with these experimental findings. In porous media convection with sub-, near- and super- critical fluid, the rapidly changing thermal diffusivity was captured by the rate the particles absorb energy. Finally, a correlation is developed allowing particle-wax T 2 relaxation time to be converted into temperature.Item Nuclear magnetic resonance studies to characterize phase transitions in porous systems(Montana State University - Bozeman, College of Engineering, 2018) Thrane, Linn Winsnes; Chairperson, Graduate Committee: Sarah L. Codd; Emily A. Berglund, James N. Wilking, David Vodak and Joseph D. Seymour were co-authors of the article, 'NMR relaxometry to characterize drug structural phase in a porous construct' in the journal 'Molecular pharmaceutics' which is contained within this thesis.; Sarah L. Codd and Joseph D. Seymour were co-authors of the article, 'Probing molecular dynamics during hydrate formation by high field NMR relaxometry and diffusometry' submitted to the journal 'Journal of magnetic resonance' which is contained within this thesis.; Ryanne L. Daily, Abby Thane, Catherine M. Kirkland, Evan R. McCarney, Robin Dykstra, Sarah L. Codd and Adrienne J. Phillips were co-authors of the article, 'Detecting microbially induced calcite precipitation in porous systems using low-field nuclear magnetic resonance relaxometry' submitted to the journal 'Environmental science & technology' which is contained within this thesis.Nuclear magnetic resonance (NMR) allows for in-situ non-invasive studies of a wide range of systems at microscopic time and length scales. NMR relaxometry and diffusometry techniques along with magnetic resonance imaging (MRI) are applied to explore and characterize various phase transitions in complex systems. NMR techniques are highly sensitive to the thermodynamic phase of the system as well as restrictions on molecular motion, and the ability to detect and monitor phase transitions non-invasively is of great interest for various industrial applications NMR frequency spectra and 1D T 2 relaxation measurements are used to characterize the presence of an amorphous drug and its liquid-solid phase transition. T 1- T 2 magnetic relaxation correlation experiments monitor the impact of long-time storage at high relative humidity on the drug in a porous silica tablet. The results indicate the ability of non-solid-state NMR to characterize crystalline and amorphous solid structural phases, and the potential for drug quality control by NMR methods. High resolution MRI along with T 1-T 2 magnetic relaxation correlation experiments and pulsed gradient stimulated echo (PGStE) NMR methods are demonstrated to characterize hydrate formation. MRI monitors the spatial heterogeneity of the system as well as local hydrate growth rates. Using T 1-T 2 correlation NMR and spectrally resolved diffusometry, the transition from mobile to restricted dynamics is observed simultaneously for both water and cyclopentane throughout the hydrate formation process. The combination of these MR techniques allows for exploration of the complex molecular dynamics involved in hydrate formation processes. Using a low-field NMR system, microbially induced calcite precipitation (MICP) processes in granular media are explored by means of 1D T 2 relaxation measurements. The 1D T 2 distributions allowed for in-situ monitoring of the mineral precipitation progress and indicates decrease in total pore volume and a significant change in the surface mineralogy of the granular media. The results confirm the potential for detailed characterization of MICP progression in engineering applications. Ultimately, NMR is demonstrated as an effective method for detecting, characterizing, and monitoring several distinct phase transitions at various time- and length-scales.Item Diffusion and diffusive exchange are sensitive to the structure of cartilage as measured by nuclear magnetic resonance(Montana State University - Bozeman, College of Engineering, 2017) Mailhiot, Sarah Elizabeth; Chairperson, Graduate Committee: Ronald K. June II; Nathan H. Williamson, Jennifer R. Brown, Joseph D. Seymour, Sarah L. Codd and Ronald K. June were co-authors of the article, 'T1-T2 correlation and biopolymer diffusion within human osteoarthritic cartilage measured with nuclear magnetic resonance' in the journal 'Applied magnetic resonance' which is contained within this thesis.; Sarah L. Codd, Jennifer R. Brown, Joseph D. Seymour and Ronald K. June were co-authors of the article, 'Pulsed gradient stimulated echo (PGSTE) NMR shows spatial dependence of fluid diffusion in human stage IV OA cartilage' submitted to the journal 'Magnetic resonance in medicine' which is contained within this thesis.; Fangrong Zong, James E. Maneval, Ronald K. June, Petrik Galvosas and Joseph D. Seymour were co-authors of the article, 'Quantifying NMR relaxation correlation and exchange in articular cartilage with time domain analysis' submitted to the journal 'Journal of magnetic resonance' which is contained within this thesis.; James E. Maneval, Ronald K. June and Joseph D. Seymour were co-authors of the article, 'Relaxation exchange in human OA cartilage impacts the observable T 2 relaxation rates' submitted to the journal 'Magnetic resonance in medicine' which is contained within this thesis.Osteoarthritis (OA) is the deterioration of the tissue on the surface of the articulating joints in mammals. OA is the progression loss of articular cartilage. OA affects 50% of people over age 65 and is the leading cause of workplace disability. There is no cure for OA and the state of the art treatment is joint replacement. One limitation for treating OA is the difficulty of diagnosing OA before tissue failure. Magnetic Resonance Imaging (MRI) is capable of detecting early pathologic changes to cartilage but challenges remain. The goal of this work is to evaluate how parameters, specifically relaxation and diffusion, used for creating imaging contrast in MRI are affected by disease in naturally occurring human osteoarthritis. Nuclear Magnetic Resonance (NMR) is utilized to measure the diffusion and magnetic relaxation in human OA cartilage samples. Diffusion Weighted Imaging (DWI) is a proposed imaging mechanism for diagnosing OA. The hypothesis is that fluid diffusion is faster in diseased tissue than in healthy tissue. We show that diffusion of fluid increases when cartilage is damaged by enzymes, such as during OA. We also show that the diffusion of fluid is donor specific in human OA cartilage. Diffusion of proteins in cartilage is also sensitive to enzyme degradation and donor as well as to the size and structure of the proteins in cartilage. These are complementary measures of the fluid and solid phase of cartilage. Relaxation weighted imaging is the most common way to image cartilage and is capable of measuring small structure changes due to OA. One limitation of this method is that reported relaxation rates vary between studies. We show that exchange, or motion of fluid, between the two sites of relaxation in cartilage alters the observed relaxation. Further, we show that the exchange rate is sensitive to donor and enzyme degradation. The results suggest that exchange rate is a sensitive measure of structure in cartilage and that relaxation should be cautiously interpreted when exchange occurs. Overall, this work shows that NMR and MRI are sensitive to the structure of cartilage and capable of detecting pathological damage to cartilage.Item Magnetic resonance studies of fluid transport in porous systems and medical devices(Montana State University - Bozeman, College of Engineering, 2017) Nybo, Elmira; Chairperson, Graduate Committee: Sarah L. Codd; Joseph D. Seymour (co-chair)This research describes the application of nuclear magnetic resonance (NMR) techniques for non-invasive investigation of fluid transport and hydrodynamics in porous systems and medical devices. NMR microscopy is used to obtain information about internal structures and transport properties in porous materials and opaque systems. Controlling dispersion within restricted pore spaces is of importance in a variety of applications including soil consolidation and dewatering and electromigration of solutes. NMR pulsed gradient stimulated echo (PGSTE) techniques combined with electroosmotic flow (EOF) are used to study diffusion and dispersion coefficients in model glass bead packs. The results show that significant EOF-induced backflow can cause structural changes and alter the flow. Understanding the transport of liquids in porous materials during the application of electrical field holds promise for solving problems involving the delivery of binding agents to infill the pore space in rigid cement-based structures via electroosmosis. NMR PGSTE techniques and micro-CT scan imaging were used to study fluid transport and structural changes in a hydrating cement paste in a closed cell. It is shown that EOF in closed cement paste samples caused a significant increase in macroscopic void volume compared to closed samples with no flow. Needleless connectors (NCs) are commonly used medical devices with complicated internal design that leads to flow complexity that may cause undesirable bacterial deposition and biofilm formation. Magnetic resonance imaging (MRI) is applied to acquire spatial velocity maps of fluid flow at various positions within the devices. MRI velocimetry is demonstrated as an effective method to quantify flow patterns and fluid dynamic dependence on structural features of NCs. Alginate and alginate-based materials find an increasing interest in environmental engineering as adsorbents for heavy metal recovery from aqueous solutions. A Ca 2+ and Cu 2+ containing fluid flow through calcium-based alginate gel has been visualized using NMR velocimetry. NMR indicated velocity changes in gel capillaries caused by ion exchange processes and followed gel structural changes. NMR microscopy is shown as an effective method to describe fluid transport and internal structural features in opaque porous systems and medical devices.Item Nuclear magnetic resonance studies of biofilm - porous media systems(Montana State University - Bozeman, College of Engineering, 2017) Kirkland, Catherine Mullinnix; Chairperson, Graduate Committee: Sarah L. Codd; Joseph D. Seymour (co-chair); Sarah L. Codd was a co-author of the article, 'Low-field borehole NMR applications in the near subsurface environment' submitted to the journal 'Vadose zone journal' which is contained within this thesis.; Randy Hiebert, Adrienne Phillips, Elliot Grunewald, David O. Walsh, Joseph D. Seymour and Sarah L. Codd were co-authors of the article, 'Biofilm detection in a model well-bore environment using low-field NMR' in the journal 'Groundwater monitoring and remediation' which is contained within this thesis.; Maria P. Herrling, Randy Hiebert, Andrew T. Bender, Elliot Grunewald, David O. Walsh and Sarah L. Codd were co-authors of the article, 'In-situ detection of subsurface biofilm using low-field NMR - a field study' in the journal 'Environmental science and technology' which is contained within this thesis.; Sam Zanetti, Elliot Grunewald, David O. Walsh, Sarah L. Codd and Adrienne J. Phillips were co-authors of the article, 'Detecting microbially-induced calcite precipitation (MICP) in a model well-bore using downhole low-field NMR' in the journal 'Environmental science and technology' which is contained within this thesis.; Jessica Weisbrodt, Catherine M. Kirkland, Nathan H. Williamson, Susanne Lackner, Sarah L. Codd, Joseph D. Seymour, Gisela Guthausen and Harald Horn were co-authors of the article, 'NMR investigation of water diffusion in different biofilm structures' submitted to the journal 'Biotechnology and bioengineering' which is contained within this thesis.Nuclear magnetic resonance (NMR) allows for in-situ non-invasive studies of opaque systems over a wide range of length and time scales, making the method uniquely suited to studies of biofilms and porous media. The research comprising this thesis uses NMR to explore biophysical, chemical, and transport properties within heterogeneous porous media systems at both a macro- and micro-scale. The macro-scale projects validate a low-field borehole NMR instrument to monitor field-scale environmental engineering applications like subsurface biofilms and microbially-induced calcite precipitation (MICP). Subsurface biofilms are central to bioremediation of chemical contaminants in soil and groundwater whereby micro-organisms degrade or sequester environmental pollutants like nitrate, hydrocarbons, chlorinated solvents and heavy metals. When composed of ureolytic microbes, subsurface biofilms can also induce calcite precipitation. MICP has engineering applications that include soil stabilization and subsurface barriers, as well as sealing of cap rocks and well-bore regions for carbon dioxide sequestration. To meet the design goals of these beneficial applications, subsurface biofilms and MICP must be monitored over space and time - a challenging task with traditional methods. The low-field borehole NMR tool recorded changes in the T 2 relaxation distribution where enhanced relaxation indicated biofilm accumulation in a sand bioreactor and in subsurface soil. Additionally, the tool was able to detect MICP in a sand bioreactor. The changed mineral surface of the sand lead to an increase in T 2 relaxation times. The complementary high-field NMR project investigated micro-scale internal structures and mass transport within biofilm granules used for wastewater treatment. Granular sludge, composed of spherical aggregates of biofilm grown without a carrier, is an innovative biological treatment method with the potential to vastly reduce the cost of wastewater treatment without sacrificing efficiency. Large gaps remain, however, in our understanding of the fundamental formation mechanisms and the factors that control granule activity and stability. Magnetic resonance imaging (MRI) identified heterogeneous internal structures within aerobic granular sludge where relaxation rates and diffusion coefficients vary. Ultimately, these results will help improve modeling for optimization of granular sludge wastewater treatment process design.Item Designing virus-like nanoparticles as T 1-enhanced MRI contrast agents(Montana State University - Bozeman, College of Letters & Science, 2014) Qazi, Shefah Alma; Chairperson, Graduate Committee: Trevor Douglas; Lars O. Liepold, Md Joynal Abedin, Ben Johnson, Peter Prevelige, Joseph A. Frank and Trevor Douglas were co-authors of the article, 'P22 viral capsids as nanocomposite high-relaxivity MRI contrast agents' in the journal 'Molecular pharmaceutics' which is contained within this thesis.; Masaki Uchida, Robert Usselman, Riley Shearer, Ethan Edwards and Trevor Douglas were co-authors of the article, 'Manganese (III) porphyrins complexed with P22 virus-like particles as T1-enhanced contrast agents for magnetic resonance imaging (MRI)' in the journal 'Journal of bioinorganic chemistry' which is contained within this thesis.; Masaki Uchida, Hisanori Kosuge, Michael V. McConnell, and Trevor Douglas were co-authors of the article, 'Expression and biophysical characterization of RGD targeting peptide on surface of P22 via C-terminus extension of DEC and P22 coat protein' which is contained within this thesis.The field of nanotechnology is a rapidly growing field. In the past few decades, nanoparticles have been utilized for use in biomedical applications with a huge impact in enhancing diagnostic techniques. Protein cages and virus-like particles are biological examples of nanoparticles. They are highly symmetric, well-defined architectures made from multiple protein subunits and can be genetically or chemically engineered to impart desired new functionalities and have been used for design of nanomaterials for improving current diagnostic techniques, as discussed in this thesis. One of the main techniques for diagnosis used today is magnetic resonance imaging (MRI) as it provides good spatial resolution of soft tissues without using harmful ionizing radiation. However, due to poor sensitivity of this technique, contrast agents are often utilized by clinicians to aid in diagnosis of diseased tissues. The main MRI contrast agents used in T1-enhanced imaging are small Gd-containing molecules. Due to the toxicity of free Gd ions, these agents are administered in a tightly chelated form. Even in this form, high doses increase the risk of toxicity. Thus, it is important to reduce overall dosage of these contrast agents. In this thesis, we discuss design principles for virus-like particle based MRI contrast agents as next generation diagnostics which can overcome the above mentioned barriers. Conjugating clinically approved contrast agents to nano-sized virus-like particles changes the intrinsic properties of the contrast agent, directly impacting and increasing MRI contrast. Modifying the interior surface of these cage-like containers to grow functionalizable polymers provides multiple sites for conjugation of small molecule contrast agents, resulting in high payload of these agents. Modifying the exterior surface of these cage-like containers to present targeting ligands and enable them to localize at desired tissues of interest. All three of these design considerations contribute to higher contrast, significantly lower clinical dose requirements, and allow for safe administration of Gd (III) ions for enhanced imaging. As gadolinium-based contrast agents are directly linked with nephrogenic systemic fibrosis, a rare but deadly disease that causes hardening of tissues and organs, an alternate low-risk metal-complex, Mn (III) porphyrins, has also been explored for bioconjugation to virus-like particles.Item From immunology to MRI data anlysis : problems in mathematical biology(Montana State University - Bozeman, College of Letters & Science, 2015) Waters, Ryan Samuel; Chairperson, Graduate Committee: Tomas GedeonThis thesis represents a collection of four distinct biological projects rising from immunology and metabolomics that required unique and creative mathematical approaches. One project focuses on understanding the role IL-2 plays in immune response regulation and exploring how these effects can be altered. We developed several dynamic models of the receptor signaling network which we analyze analytically and numerically. In a second project focused also on MS, we sought to create a system for grading magnetic resonance images (MRI) with good correlation with disability. The goal is for these MRI scores to provide a better standard for large-scale clinical drug trials, which limits the bias associated with differences in available MRI technology and general grader/participant variability. The third project involves the study of the CRISPR adaptive immune system in bacteria. Bacterial cells recognize and acquire snippets of exogenous genetic material, which they incorporate into their DNA. In this project we explore the optimal design for the CRISPR system given a viral distribution to maximize its probability of survival. The final project involves the study of the benefits for colocalization of coupled enzymes in metabolic pathways. The hypothesized kinetic advantage, known as 'channeling', of putting coupled enzymes closer together has been used as justification for the colocalization of coupled enzymes in biological systems. We developed and analyzed a simple partial differential equation of the diffusion of the intermediate substrate between coupled enzymes to explore the phenomena of channeling. The four projects of my thesis represent very distinct biological problems that required a variety of techniques from diverse areas of mathematics ranging from dynamical modeling to statistics, Fourier series and calculus of variations. In each case, quantitative techniques were used to address biological questions from a mathematical perspective ultimately providing insight back to the biological problems which motivated them.Item Heterologous expression of laminin peptide 11 on a virus particle surface for use in malignant tumor cell targeting(Montana State University - Bozeman, College of Letters & Science, 2000) Arnold, Thomas DarmodyItem Exploring the potential of protein cages as MRI contrast agents with an emphasis on protein cage characterization by mass spectrometry techniques(Montana State University - Bozeman, College of Letters & Science, 2009) Liepold, Lars Otto; Chairperson, Graduate Committee: Trevor Douglas; Mark J. Young (co-chair)Described here is the development of a protein cages as efficient and potentially relevant MRI contrast agents. Three approaches are outlined to fuse high affinity Gd³+ chelating moieties to the surfaces of protein cages. In the first approach, a metal binding peptide has been genetically engineered into the subunit of Cowpea chlorotic mottle virus (CCMV) and to the small heat shock protein cage from Methanococcus jannaschii (HSP). The genetic fusion resulted in a 200x binding enhancement of Gd³+ to CCMV in comparison with wild type CCMV and metal binding functionality was added to the HSP protein cage. In a second approach DOTA-Gd was attached to CCMV by reactions with endogenous lysine residues on the surface of the viral capsids and resulted in r1 = 2,806 at 61 MHz for the 28nm diameter particle. Directed by the results of earlier generations of protein cage based contrast agents a next generation MRI contrast agent was designed. In this work a DTPA-Gd containing polymer was grown in the interior of HSP resulting in T1 particle relaxivities of 4,200mM-¹ sec-¹ for the 12nm particle. Relaxivity parameters were determined and this analysis suggests that the rotational correlation time of the Gd³+ chelate has been optimized while the exchange life time of Gd³+-bound water is slower than optimal. This synthetic approach holds much promise for the development of future generations of contrast agents. Throughout the evolution of the protein cage based contrast agents there has also been and evolution of our ability to characterize these cages with mass spectrometric techniques. Specifically refined methodologies are presented for QTof characterization of protein cage at the level of amino acids, protein subunits, protein complexes and their cellular expression. Furthermore, correct charge state assignment is crucial to assigning an accurate mass to supramolecular complexes such as protein cages analyzed by electrospray mass spectrometry. Conventional charge state assignment techniques fall short of reliably and unambiguously predicting the correct charge state for many supramolecular complexes. We provide an explanation of the shortcomings of the conventional techniques and have developed a robust charge state assignment method that is applicable to all spectra.