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Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder. Cortical thinning of the anterior mid-cingulate cortex (aMCC) and insula has been previously reported in IBS (Davis et al., 2008). The aim of the present study was to examine cortical and subcortical structural gray matter integrity in IBS with particular attention to individual disease symptoms and personality characteristics such as pain catastrophizing. Eleven IBS patients and 16 age-matched healthy subjects (female, right-handed) underwent structural MRI. Voxel Based Morphometry and Cortical Thickness Analysis revealed that the IBS group had increased gray matter density in the hypothalamus, cortical thinning in the aMCC, strong (r = -66; p=0.015), a negative correlation between dorsolateral prefrontal cortex and pain catastrophizing and anterior insula thickness was positively correlated to pain duration (r = 0.77, p=0.003) when controlling for age. These abnormalities may contribute to chronic pain in IBS.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder. Cortical thinning of the anterior mid-cingulate cortex (aMCC) and insula has been previously reported in IBS (Davis et al., 2008). The aim of the present study was to examine cortical and subcortical structural gray matter integrity in IBS with particular attention to individual disease symptoms and personality characteristics such as pain catastrophizing. Eleven IBS patients and 16 age-matched healthy subjects (female, right-handed) underwent structural MRI. Voxel Based Morphometry and Cortical Thickness Analysis revealed that the IBS group had increased gray matter density in the hypothalamus, cortical thinning in the aMCC, strong (r = -66; p=0.015), a negative correlation between dorsolateral prefrontal cortex and pain catastrophizing and anterior insula thickness was positively correlated to pain duration (r = 0.77, p=0.003) when controlling for age. These abnormalities may contribute to chronic pain in IBS.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Computer tomography (CT) is commonly used to evaluate suspected acute appendicitis; however, ionizing radiation limits its use in children. This study assesses 3T magnetic resonance imaging (MRI) as an imaging modality in the evaluation of suspected acute appendicitis in the pediatric population. This study is a retrospective review of prospectively‐collected data from 155 pediatric subjects who underwent MRI and 197 pediatric subjects who underwent CT for suspected acute appendicitis. Sensitivity, specificity, appendix visualization rate, positive appendicitis rate, and alternative diagnosis rate are determined. Sensitivity and specificity of MRI are 100% and 98%, 99% and 97% for CT (p = 0.61 and 0.53), respectively. Appendix visualization rate is 77% for MRI, 90% for CT (p = 0.0002), positive appendicitis rate is 25% for MRI, 34% for CT (p = 0.175), and alternative diagnosis rate is 3% for MRI, 3% for CT (p = 0.175). This study supports 3T MRI as a comparable modality to CT in the evaluation of suspected acute appendicitis in the pediatric population. Although MRI visualizes the appendix at a lower rate than CT, our protocol maintains 100% sensitivity with no false negatives. Our appendix visualization rate with 3T MRI (77%) is an improvement from published data from both 1.5T and 3T MRI systems. The exam time differential is clinically insignificant and use of MRI spares the patient the ionizing radiation and intravenous contrast of CT.

Since the development of magnetic resonance imaging (MRI), there have been many novel advances in our understanding of brain structure and function. More recently, functional MRI has revealed networks of spatially isolated brain regions with temporally correlated activity, forming resting state networks. Research has long shown that mindfulness can produce psychological improvements. A new wave of research is demonstrating how mindfulness is associated with alterations in these brain networks. The current thesis examined changes in patterns of functional connectivity associated with scores from a commonly used mindfulness questionnaire in three resting state networks: the default mode network, the central executive network, and the salience network. Independent component analysis data from 32 healthy participants revealed that mindfulness is associated with altered patterns of functional connectivity in all three networks. For example, decreased connectivity was observed in the precuneus in two of the networks, a region associated with mind wandering. This suggests that mindfulness has a physiological influence on the resting state functional connectivity of the brain that coincides with the underlying principles of mindfulness. / May 2017

The ability to grow materials in the nanometric size regime with controlled shape and size provide a fundamental synthetic challenge, while allowing for evaluation of such unique nanostructures in multiple applications. In this dissertation, colloidal sodium lanthanide fluoride (NaLnF4) nanocrystals are described with an overall emphasis on i) size control, ii) surface chemistry related towards their applications as nano-bioprobes, and iii) the synthesis and fundamental aspects of epitaxial layer growth generally referred as core-shell nanocrystals. Chapter 1 provides a brief overview on the basic aspects of colloidal nanocrystals. In Chapter 2, synthesis and surface modification of colloidal sodium lanthanide fluoride nanocrystals, epitaxial growth, and their applications in optical and magnetic resonance imaging is reviewed. Chapter 3 describes a phase transfer protocol utilizing polyvinylpyrrolidone and subsequent silica coating of initially hydrophobic upconverting nanocrystals. This protocol is extended in Chapter 4 using end-group functionalized polyvinylpyrrolidone and demonstrates tunability of surface charge and functional groups on upconverting nanocrystals for targeted labeling of human prostate cancer cells. The synthesis of size-tunable NaGdF4 nanocrystals below 10 nm is described in Chapter 5. These nanocrystals are evaluated for their efficacy in magnetic resonance imaging (MRI), and a fundamental insight into the effect of surface gadolinium ions in T1 MRI contrast enhancement is presented. Chapter 6 demonstrates the synthesis of tunable, epitaxial layers on upconverting (core) nanocrystals. A novel synthetic strategy is demonstrated, by deliberate defocusing and self-focusing of differently sized nanocrystals driven by the common physical phenomenon of Ostwald ripening. Utilizing the contraction of lanthanide ions along the series, a fundamental investigation on the effect of compressive/tensile strain epitaxial layer growth is presented in Chapter 7. The fundamental rule of minimal lattice mismatch for epitaxial growth takes into account only the magnitude of mismatch and not the sign of mismatch caused by a compressive/tensile strained layer. A strong asymmetric effect between the compressive/tensile layer growth given the same magnitude of lattice mismatch is observed, demonstrating the necessity of including the sign of mismatch to generate isotropic (conformal)/ pseudomorphic (coherent) epitaxial growth. Finally, in Chapter 8 conclusions and possible future work are discussed. / Graduate / 0494

Background: To describe the scoring methodology and MRI assessments used to evaluate the cross-sectional features observed in cases and controls, to define change over time for different MRI features, and to report the extent of changes over a 24-month period in the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium study nested within the larger Osteoarthritis Initiative (OAI) Study. Methods: We conducted a nested case-control study. Cases (n = 406) were knees having both radiographic and pain progression. Controls (n = 194) were knee osteoarthritis subjects who did not meet the case definition. Groups were matched for Kellgren-Lawrence grade and body mass index. MRIs were acquired using 3 T MRI systems and assessed using the semi-quantitative MOAKS system. MRIs were read at baseline and 24 months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. We provide the definition and distribution of change in these biomarkers over time. Results: Seventy-three percent of the cases had subregions with BML worsening (vs. 66 % in controls) (p = 0.102). Little change in osteophytes was seen over 24 months. Twenty-eight percent of cases and 10 % of controls had worsening in meniscal scores in at least one subregion (p < 0.001). Seventy-three percent of cases and 53 % of controls had at least one area with worsening in cartilage surface area (p < 0.001). More cases experienced worsening in Hoffa- and effusion synovitis than controls (17 % vs. 6 % (p < 0.001); 41 % vs. 18 % (p < 0.001), respectively). Conclusions: A wide range of MRI-detected structural pathologies was present in the FNIH cohort. More severe changes, especially for BMLs, cartilage and meniscal damage, were detected primarily among the case group suggesting that early changes in multiple structural domains are associated with radiographic worsening and symptomatic progression.

Background: Given that individuals with subjective cognitive decline (SCD) report a change that is not yet measurable with standard neuropsychological assessment measures, they are thought to be the earliest along the cognitive continuum between healthy aging and Alzheimer’s disease (AD). The current study used a neuroimaging approach to examine differences in brain function and structure between individuals with SCD and healthy controls (HC). Method: 3T resting state functional MRI and high resolution anatomical images were retrieved from 23 individuals with SCD (mean age = 72.9 years, SD = 5.4, 12 females) and 23 HC (mean age = 74.3 years, SD = 5.0, 12 females) from the screening time point from the AD Neuroimaging Initiative database. All data were processed using the FMRIB Software Library. Seed-based analyses of the default mode network (DMN) were used to compare differences in brain function between SCD and HC groups (Z > 2.3; cluster significance: p < 0.05, corrected). Voxel-based morphometry (VBM) was used to examine differences in grey matter volume between the SCD and HC groups. Results: The SCD and HC groups were not significantly different in age or education level. Results revealed significantly greater activity in the DMN including the bilateral precuneus cortex, bilateral thalamus, and right hippocampal regions in individuals with SCD relative to controls. Conversely, those with SCD showed decreased activation in the bilateral frontal pole, caudate, angular gyrus, lingual gyrus, right superior frontal gyrus, right occipital pole, right superior temporal gyrus, left superior temporal gyrus in the posterior division, left precuneus cortex, left precentral gyrus, left occipital fusiform gyrus, left temporal pole, and left cerebellum compared to HC. Finally, VBM results did not show significant differences in grey matter volume between the groups. Conclusion: Findings revealed changes in brain function but not structure between individuals with SCD and HC. Overall, this study represents a crucial step in characterizing individuals with SCD, a group recognized to be at increased risk for AD. It is imperative to identify biomarkers prior to significant decline on clinical assessment, so that disease-delaying interventions may be delivered at the earliest possible time point. / Graduate / 2020-08-15

"Magnetic resonance imaging (MRI) has emerged as the imaging modality of choice in a wide variety experimental and clinical applications. In this dissertation, I will describe novel MRI techniques for the characterization of neural and pulmonary vascular function in preclinical models of disease. In the first part of this dissertation, experimental results will be presented comparing the identification of ischemic lesions in experimental stroke using dynamic susceptibility contrast (DSC) and a well validated arterial spin labeling (ASL). We show that DSC measurements of an index of cerebral blood flow are sensitive to ischemia, treatment, and stroke subregions. Further, we derived a threshold of cerebral blood flow for ischemia as measured by DSC. Finally, we show that ischemic lesion volumes as defined by DSC are comparable to those defined by ASL. In the second part of this dissertation, a methodology of visualizing clots in experimental animal models of stroke is presented. Clots were rendered visible by MRI through the addition of a gadolinium based contrast agent during formation. Modified clots were used to induce an experimental embolic middle cerebral artery occlusion. Clots in the cerebral vasculature were visualized in vivo using MRI. Further, the efficacy of recombinant tissue plasminogen activator (r-tPA) and the combination of r-tPA and recombinant annexin-2 (rA2) was characterized by clot visualization during lysis. In the third part of this dissertation, we present results of the application of hyperpolarized helium (HP-He) in the characterization of new model of experimental pulmonary ischemia. The longitudinal relaxation time of HP-He is sensitive to the presence of paramagnetic oxygen. During ischemia, oxygen exchange from the airspaces of the lungs to the capillaries is hindered resulting in increased alveolar oxygen content which resulted in the shortening of the HP-He longitudinal relaxation time. Results of measurements of the HP-He relaxation time in both normal and ischemic animals are presented. In the final part of this dissertation, I will present results of a new method to measure pulmonary blood volume (PBV) using proton based MRI. A T1 weighted, inversion recovery spin echo sequence with cardiac and respiratory gating was developed to measure the changes in signal intensity of lung parenchyma before and after the injection of a long acting intravascular contrast agent. PBV is related to the signal change in the lung parenchyma and blood before and after contrast agent. We validate our method using a model of hypoxic pulmonary vasoconstriction in rats."

Magnetic Resonance Imaging (MRI) is a widely used soft-tissue imaging modality that has evolved over the past several years into a powerful and versatile medical diagnostic tool capable of providing in-vivo diagnostic images of human and animal anatomies. Current research efforts in MRI system design are driven by the need to obtain detailed high resolution images with improved image signal-to-noise ratio (SNR) at a given magnetic field strength. Invariably, this requirement demands the development of high performance MRI radio frequency (RF) coils. However, the complexities and stringent requirements of modern clinical MRI systems necessitate the development of new modeling methodologies for the design of high performance RF coils. This dissertation addresses this need by developing a distinct Method of Moments (MoM) modeling approach suitable for the simulation of RF coils loaded with biological tissues. The unique implementation utilizes two distinct basis functions in order to collectively describe the surface current density on the RF coil, and the sum of the volume current density and the displacement current density in the associated biological tissue. By selecting basis functions with similar properties to the actual physical quantities they describe, we avoided spurious solutions normally associated with MoM based implementations. The validity of our modeling method was confirmed by comparisons with analytical solutions as well as physical measurements, yielding good agreement. Furthermore, we applied the MoM based modeling method in the design and development of a novel 4-channel receive-only RF coil for breast imaging in a clinical 1.5T system. The new coil design was inspired by the multi-channel array concept, where multiple conducting strips were arranged in an anatomically conforming profile with the intention of improving sensitivity and SNR. In addition, the coil structure featured an open breast coil concept in order to facilitate MRI-guided biopsy and patient comfort. A comparison of simulation results and actual physical measurements from the prototype RF coil demonstrated good agreement with one another. Also, imaging tests were conducted on a pair of MRI phantoms as well as on a human patient after obtaining proper authorization. The tests revealed good magnetic field homogeneity and a high SNR in the region of interest. In addition, performance comparisons between the prototype 4-channel RF coil and existing high end clinical 4-channel RF breast coils indicated an achievement of superior SNR in conjunction with very good magnetic field homogeneity. Currently, the prototype 4-channel RF coil has outperformed all existing high end clinical 4-channel RF coils used in comparison studies.