Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
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Item Image Reconstruction for Hyperpolarized Carbon-13 Metabolic Magnetic Resonance Imaging with Iterative Methods(2024) Zhu, Minjie; Babadi, Behtash; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Magnetic resonance imaging (MRI) with hyperpolarized carbon-13 (13C) agents is an emerging in vivo medical imaging technique. 13C MRI gives a series of images that show the evolution of the injected substrate and its metabolic products in the imaging volume, which leads to various medical applications including monitoring tumor progression and post-treatment response in both animal models and clinical trials. This dissertation focuses on the application of novel iterative image reconstruction methods for 13C MRI that aim to improve image quality and temporal resolution.One of the challenges for the existing 13C MRI reconstruction method is the difficulty in quantification of lower intensity metabolites due to noise and overlapping peaks in the aliased spectrum. In the first part of the dissertation, a model-based iterative reconstruction method is proposed to overcome such difficulty. The proposed method utilizes prior knowledge of the properties of the metabolites in the imaging volume, including off-resonance frequency, T2* decay constants, and the image acquisition trajectory in spatial and frequency domain. Metabolic images are reconstructed through solving the linear equation between acquired signal and images with least square error estimation. The reconstruction results on in vivo imaging data sets demonstrate that the proposed method can separate two overlapped peaks in an aliased spectrum while the conventional method fails. Another challenge for 13C MRI is to reconstruct metabolic images from under-sampled acquisitions. Due to the short lifetime of the injected substrate and the physical limitation of the MRI scanner, only a few temporal frames can be acquired for 13C MRI with one injection. Under-sampling in the image acquisition can provide more frames, but certain reconstruction methods are required to remove the artifacts from direct reconstruction on the under-sampled data. In the second part of the dissertation, a customized low-rank plus sparse (L+S) reconstruction method is proposed to produce artifact-free images from under-sampled data. Digital phantom simulations are performed to evaluate the optimal reconstruction parameters. Simulation with digital phantom and in vivo mouse imaging on 2D and 3D dynamic imaging data demonstrate the effectiveness in acceleration without introducing image artifacts using the proposed reconstruction method. In the third part of the dissertation, we present a preclinical application of 13C MRI to study brain metabolism and identify the source of metabolic products based on the metabolic images derived. In vivo metabolic imaging with different flow-suppression levels was performed on rats in the brain region. Results show that metabolic product, lactate, has no significant dependence on the level of suppression while the substrate pyruvate is strongly dependent. This supports our hypothesis that lactate seen in metabolic images is generated in the brain. Additional high-resolution metabolic imaging was performed to show different signal distributions for pyruvate and lactate clearly. Our proposed L+S reconstruction method was applied to the dynamic image data to reduce the background noise. The derived dynamic images show distinct dynamics for pyruvate and lactate, further supporting our hypothesis.Item Assessing the Impact of Typical Variations in Stressful Life Events on Hippocampal Development in Childhood(2021) Botdorf, Morgan; Riggins, Tracy; Psychology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The negative impact of extreme stress on early brain development is well-documented. An emerging body of work suggests that less extreme and more typical variations in stressful experiences (e.g., parental divorce, changing schools) may also exert an impact on the brain, especially in early childhood; however, more systematic research is needed. Across, three studies, this dissertation addressed this gap by exploring effects of typical variations in stressful life events on development of the hippocampus, a brain region highly susceptible to stress. Study 1a assessed the impact of stressful life events on the development of hippocampal subfield volumes (i.e., CA1, CA2-4/dentate gyrus (DG), subiculum) in an accelerated longitudinal sample of 102 4- or 6-year-old children who were each followed for 3 years. Analyses revealed that experiencing more stressful life events was related to smaller CA1 and CA2-4/DG volumes in the 6- (but not 4-) year-old cohort. Study 1b used the same sample described in Study 1a to investigate the impact of stressful life events on functional connectivity between the hippocampus and stress-related cortical regions. Analyses revealed a significant association in the 4- (but not 6-) year-old cohort, such that experiencing more stressful life events was related to greater connectivity between the hippocampus and the insula, a region important for emotional processing. Study 2 assessed moderating effects of sex and socioeconomic status (SES) on the association between stressful events and hippocampal subfield volumes using a large (n = 4,348), diverse subsample of 9-10-year-old adolescents from the Adolescent Brain and Cognitive Development Study. Analyses revealed that stressful life events were related to smaller subiculum volumes, but these associations did not vary by sex or SES. Overall, these findings provide evidence of the impact of typical variations in stressful life events on both hippocampal structure and functional connectivity. Findings also highlight the complexity of stress effects on the brain as these experiences may impact the hippocampus in an age-dependent manner. These results advance our current understanding of how stress influences hippocampal development and pave the way for studies to assess the implications of findings both for cognitive processes and the development of stress-related disorders.Item HIPPOCAMPAL SUBREGION VOLUME IN HIGH-RISK OFFSPRING PREDICTS INCREASES IN DEPRESSIVE SYMPTOMS ACROSS THE TRANSITION TO ADOLESCENCE(2020) Hubachek, Samantha Qirko; Dougherty, Lea R.; Psychology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The hippocampus has been implicated in the pathophysiology of depression. This study examined whether youth hippocampal subregion volumes were differentially associated with maternal depression history and youth’s depressive symptoms across the transition to adolescence. 74 preadolescent offspring (Mage=10.74+/-.84 years) of mothers with (n=33) and without a lifetime depression history (n=41) completed a structural brain scan. Youth depressive symptoms were assessed prior to the neuroimaging assessment at age 9 (Mage=9.08+/-.29 years), at the neuroimaging assessment, and in early adolescence (Mage=12.56+/-.40 years). Maternal depression was associated with preadolescent offspring’s reduced bilateral hippocampal head volumes and increased left hippocampal body volume. Reduced bilateral head volumes were associated with offspring’s increased concurrent depressive symptoms. Furthermore, reduced right hippocampal head volume mediated associations between maternal depression and increases in offspring depressive symptoms from age 9 to age 12. Findings implicate reductions in hippocampal head volume in the intergenerational transmission of risk from parents to offspring.Item QUANTITATIVE STUDY OF LONGITUDINAL RELAXATION (T1) CONTRAST MECHANISMS IN BRAIN MRI(2017) Jiang, Xu; Anlage, Steven M.; Physics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Longitudinal relaxation (T1) contrast in MRI is important for studying brain morphology and is widely used in clinical applications. Although MRI only detects signals from water hydrogen (1H) protons (WPs), T1 contrast is known to be influenced by other species of 1H protons, including those in macromolecules (MPs), such as lipids and proteins, through magnetization transfer (MT) between WPs and MPs. This complicates the use and quantification of T1 contrast for studying the underlying tissue composition and the physiology of the brain. MT contributes to T1 contrast to an extent that is generally dependent on MT kinetics, as well as the concentration and NMR spectral properties of MPs. However, the MP spectral properties and MT kinetics are both difficult to measure directly, as the signal from MPs is generally invisible to MRI. Therefore, to investigate MT kinetics and further quantify T1 contrast, we first developed a reliable way to indirectly measure the MP fraction and their exchange rate with WPs, with minimal dependence on the spectral properties of MPs. For this purpose, we used brief, high-power radiofrequency (RF) NMR excitation pulses to almost completely saturate the magnetization of MPs. Based on this, both MT kinetics and the contribution of MPs to T1 contrast through MT were studied. The thus obtained knowledge allowed us to subsequently infer the spectral properties of MPs by applying low-power, frequency-selective off-resonance RF pulses and measuring the offset-frequency dependent effect of MPs on the WP MRI signal. A two-pool exchange model was used in both cases to account for direct effects of the RF pulse on WP magnetization. Consistent with earlier works using MRI at low-field and post-mortem analysis of brain tissue, our novel measurement approach found that MPs constitute an up to 27% fraction of the total 1H protons in human brain white matter, and their spectrum follows a super-Lorentzian line with a T2 of 9.6±0.6 μs and a resonance frequency centered at -2.58±0.05 ppm, at 7 T. T1 contrast was found to be dominated by MP fraction, with iron only modestly contributing even in the iron-rich regions of brain.Item BIOMIMETIC NANOSTRUCTURES FOR THERANOSTIC APPLICATIONS(2015) Kuo, Yuan-Chia; D'Souza, Warren D; Raghavan, Srinivasa R; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Theranostic nanostructures are those that have both therapeutic as well as diagnostic function, e.g., due to having a combination of drugs as well as imaging agents in them. Such structures, especially those that can selectively home in on cancer tumors, have received considerable attention recently. Although many different structures have been synthesized, their complexity, high cost, and poor biocompatibility have limited their clinical application. In this study, we focus on creating new classes of theranostic nanostructures using simple routes (via self-assembly) and utilizing inexpensive and biocompatible materials. In our first study, we describe a class of liposomal probes that can allow certain tumors to be imaged by magnetic resonance imaging (MRI). Tumors, such as those of head and neck cancer, are known to over-express the epidermal growth factor receptor (EGFR). Our liposomal probes bear anti-EGFR antibodies as well as chelated gadolinium (Gd), a positive (image-brightening) contrast agent for MRI. To synthesize these probes, we use a strategy that is carefully designed to be simple and scalable: it employs two steps that each involve self-assembly. The resulting probes bind in vitro to EGFR-overexpressing tumor cells compared to controls. Moreover, cancer cells with bound probes can be tracked by MRI. In the future, these probes could find clinical use for tracking the efficacy of cancer treatment in real-time. Next, we report a class of microscale (3 to 5 µm) containers derived from erythrocytes (red blood cells). Micro-erythrosomes (MERs) are produced by emptying the inner contents of these cells (specifically hemoglobin) and resuspending the empty structures in buffer. We have developed procedures to functionalize the surfaces of the MERs with targeting moieties (such as anti-EGFR antibodies) and also to load solutes (such as fluorescent dyes and MRI contrast agents) into the cores of the MERs. Thus, we show that MERs are a versatile class of microparticles for biomedical applications. In our final study, we show that the MERs from the previous study can be sonicated to yield nanoscale structures, termed nano-erythrosomes (NERs), with average sizes around 120 nm. NERs are membrane-covered nanoscale containers, much like liposomes. They show excellent colloidal stability in both buffer as well as in serum at room temperature, and they are able to withstand freeze-thaw cycling. Moreover, NER membranes can be decorated with fluorescent markers and antibodies, solutes can be encapsulated in the cores of the NERs, and NERs can be targeted towards mammalian cells. Thus, NERs are a promising and versatile class of nanostructures for use in nanomedicine.Item Aging Related Differences in Hand Intrinsic and Extrinsic Muscles for Hand Dexterity: An MRI Investigation(2009) Hsu, Jeffrey; Shim, Jae Kun; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Hand dexterity is crucial for humans to interactions with the external environment. Many activities of daily living (ADLs) such as pressing, grasping, writing and typing would be unattainable without a skillfully and proficiently functioning hand. Sexagenarians and older often experience difficulties in hand dexterity, which seriously impair their ability to perform ADLs. This study described the aging-related changes in hand muscle size and dexterity; and addressed the conflicting literature regarding the extent of atrophy to either the intrinsic or extrinsic hand muscles in the elderly. The overall hypotheses for this study were 1) that elderly adults show an aging-related decrease in hand muscle size and strength, especially a greater decrease in the intrinsic hand muscles, 2) elderly adults show an aging-related decrease in hand dexterity and 3) hand muscle size and strength are positively related to hand dexterity. This study examined hand muscle sizes with magnetic resonance imaging (MRI) and examined hand strength and other functional measures. This study found aging-related decreases in muscle size, muscle strength, hand dexterity. Furthermore, intrinsic muscles showed a greater aging-related decrease in volume and strength as compared to the extrinsic muscles. When examining relationships, muscle strength was positively correlated to multi-finger synergy and finger dependence. Also, muscle size was positively related to performance on clinical hand dexterity tests. This supports the strength-dexterity equivalence hypothesis.Item PROSPECTIVE HEAD MOVEMENT CORRECTION FOR HIGH-RESOLUTION MRI USING AN IN-BORE OPTICAL TRACKING SYSTEM(2009) Qin, Lei; Tao, Yang; Biological Resources Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In MRI of the human brain, subject motion is a major cause of magnetic resonance image quality degradation. To compensate the effects of head motion during data acquisition, an in-bore optical motion tracking system is proposed. The system comprises one or two MR compatible infrared cameras that are fixed on a holder right above and in front of the head coil. The resulting close proximity of the cameras to the object allows precise tracking of its movement. During image acquisition, the MRI scanner uses this tracking information to prospectively compensate for head motion by adjusting gradient field direction and RF phase and frequency. Experiments performed on subjects demonstrate the system's robustness, exhibiting an accuracy of better than 0.1mm and 0.15˚.Item Hydromagnetic turbulent instability in liquid sodium experiments(2004-04-30) Sisan, Daniel R; Lathrop, Daniel P; PhysicsThis dissertation describes the observation of magnetically-induced instabilities that occur from a preexisting hydrodynamically turbulent background. We claim these instabilities are the first direct observation of the magneto-rotational instability (MRI). An extensive body of theoretical and numerical research has established the MRI is important in the theory of accretion disks: magnetic fields destabilize otherwise stable astrophysical flows, causing turbulence and an increased angular momentum transport needed for accretion. Our instabilities occur in liquid sodium between differentially rotating concentric spheres (spherical Couette flow) where an external field is applied parallel to the axis of rotation. Our experiments are also the first known spherical Couette flow in an electrically conducting fluid, and only the second experiment, in any fluid, at an aspect ratio of 2, the same of the Earth's core. We describe the development of a Hall probe array that measures the field at 30 points outside the sphere and is used to perform a spherical harmonic decomposition (up to l=4) of the induced field. We present measurements taken with this array, along with measurements of torque needed to spin the inner sphere and of the flow velocity using ultrasound doppler velocimetry. Our experiment is consistent with prior theory, even though our instabilities occur in the presence of preexisting hydrodynamic turbulence (the theory starts with an initially laminar flow). This result may be particularly relevant in light of an ongoing debate on whether accretion disks are hydrodynamically unstable independent of external fields. The most important contribution of our experiments, however, may be in providing data with which to benchmark the many numerical and theoretical studies of the MRI and the codes used to simulate the Earth's core.