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Item A 24-channel radio frequency receive array for magnetic resonance imaging of primates at 10.5 T(2023-08) Jungst, SteveMagnetic resonance imaging (MRI) is a unique modality which offers many advantages and challenges compared to other imaging technologies. The radio frequency (RF) coil is one of the key hardware sub-systems, which drives overall MRI system performance to enable higher resolution imaging and the collection of high fidelity information about organism structure and function. To optimize RF coil performance, notably the signal-to-noise ratio (SNR) of the received signal, it is imperative that each coil be custom made to the specific static field strength of the MRI system, the anatomical region of interest, and the desired experimental constraints. This thesis explores some of the technical underpinnings of MRI with a focus on RF coil construction for non-human primate (NHP) imaging. A 24-channel RF receive array coil with integrated transmitter is presented, followed by a discussion of its performance, imaging results, and future directions.Item Adaptation of advanced MRI and NMR technique for low magnetic field MRI system.(2012-07) Li, YunNuclear magnetic resonance techniques, including nuclear magnetic imaging (MRI) and nuclear magnetic resonance (NMR) relaxometry are increasingly gaining interest and acceptance by food scientists and engineers. These techniques are being used to study moisture and fat content, water mobility, and distribution of water, fat, and temperature in foods. They are also used to determine freezing front and viscosity of foods. A unique advantage of NMR techniques is their non-invasive and non-destructive nature, making analysis faster and more reliable than conventional techniques. MRI work in the food area is primarily conducted using expensive and hard to operate large MRI systems. Most food companies, especially small companies, are not willing to use or cannot afford such large systems. Therefore, developing small systems specifically for food samples is an urgent need. NMR relaxometry has been used by food scientists for decades. However, only recently food scientists began to realize that the technique has more to offer. Research on the relationship between NMR relaxation times and physiochemical properties of foods is emerging. A suite of techniques were developed for the acquisition of reliable data and high quality images using low field MRI machines. My research has helped solve some key technical problems by improving the hardware configuration, pulse sequences, and data analysis techniques. In my research, advanced pulse sequences were adapted to our low field MRI machines for MRI imaging work and NMR relaxation work. Pulse sequences were tuned to obtain high quality images. New hardware was developed to accommodate unique samples. New NMR data acquisition schemes and data analysis techniques were developed to obtain additional information for the analysis of food stability. Models were designed for state diagrams. Coding programs were developed to calculate and analyze state diagram related parameters. My work involved both hardware and software improvements to facilitate adaptation and implementation of advanced techniques. It is my hope that these low field MRI machines be improved through my study so that they become an affordable, easy-to-operate, and relatively maintenance free analytical tool for food research and development and quality control labs.Item Advanced methodologies for neuromodulation and quantitative MRI with MB-SWIFT(2023) WU, LinIntroduction: Deep Brain Stimulation (DBS) treatment for Alzheimer’s disease (AD) is becoming increasingly evident. In this study, we exploited a novel orientation-selective (OS) strategy recently introduced by our group for DBS, entitled orientation-selective DBS (OS-DBS). This strategy entails that, by using multiple contacts with independent current sources within a multi-electrode array, the electric field can be oriented along any desired orientation in space. Therefore, axons parallel to the electric field spatial gradients are preferentially activated. Moreover, we applied the OS methodology to epidural spinal cord stimulation. In order to detect pathological processes of AD non-invasively with magnetic resonance imaging (MRI) technology, an alternating Look-Locker (aLL) method was developed to study novel MRI biomarkers such as T1? based on rotating frame MRI methods tailored to reveal neurodegeneration. Objectives and Methods: 1) For OS-ESCS, we introduced a similar OS approach for ESCS, and demonstrated orientation dependent brain activations as detected by brain fMRI. 2) To study OS-DBS of the subthalamic nucleus (STN), AD related targets including the entorhinal cortex (EC) and medial septal nucleus (MSN), to demonstrate the basic principle of OS and prove its feasibility and advantage in optimizing the stimulation of the target. Here, OS-DBS with a three-channel electrode was utilized to stimulate the rat STN, EC, and MSN to modulate the activation of brain networks connected to the stimulation sites. The induced brain activity was monitored with fMRI by Multi-Band Sweep Imaging with Fourier Transformation (MB-SWIFT) readout at 9.4 T. 3) The aLL method was proposed to perform simultaneous quantitative T1 and T1?, or T1 and B1 3D MRI mapping. Look-Locker scheme that alternates magnetization from the laboratory frame’s +Z and -Z axes is combined with a 3D MB-SWIFT readout. The analytical solution describing the spin evolution during aLL and the correction required for segmented acquisition were derived. The simultaneous B1 and T1 mapping were demonstrated on a phantom. T1? values in the rat brain in vivo and the Gd-DTPA phantom were compared to those obtained with a previously introduced steady–state (SS) method. Results: 1) For ESCS, orientation dependent activations were detected in brain areas that transmit the motor and sensory information. 2) OS-DBS of the STN reached maximal activation of related brain areas in correspondence with an in-plane 180° stimulation angle, which was consistent with the main mediolateral direction of the STN fibers confirmed with high resolution diffusion imaging and histology. Varying the in-plane OS-DBS stimulation angle in the EC resulted in the modulation of multiple downstream brain areas involved in memory and cognition. In contrast, no angle dependence of brain activation was observed when stimulating the MSN, consistent with predictions based on the electrode configuration and on the main axonal directions of the targets derived from diffusion MRI tractography and histology. 3) The aLL method allows for simultaneous T1 and B1 mapping, while the aLL method with the application of MP modules can provide simultaneous T1 and T1? maps. T1? values were similar with both aLL and SS techniques. However, aLL resulted in more robust quantitative mapping as compared with the SS method and provided the advantage of generating T1 maps in a single acquisition. Conclusions: 1) OS-ESCS allows the targeting of spinal fibers of different orientations, ultimately making stimulation less dependent on the precision of the electrode implantation. 2) OS-DBS stimulation angle modulates the activation of brain areas relevant to AD and Parkinson’s disease (PD), thus holding great promise for DBS treatment of the diseases. 3) The proposed aLL method offers a new flexible tool for quantitative T1, T1?, and B1 mappings.Item Application of Parallel Transmission to Ultra-High Field Magnetic Resonance Spectroscopy and Imaging(2022-03) He, XiaoxuanMagnetic resonance imaging is a non-invasive imaging technology that produces detailed images of biological tissue with anatomical and functional information. While the use of ultra-high field helps improve the sensitivity of MRI, one major challenge of imaging at such extreme field strength is the transmit B1 field inhomogeneity. The technique of parallel transmission has been proposed to mitigate such challenge and provides opportunities to explore new acquisition methods. To take advantage of these capabilities, this thesis investigates its application to spectroscopy and imaging at ultra-high field consisting of the following three projects. First, a novel spectroscopy acquisition method is proposed featuring the use of a parallel transmit optimized 3D adiabatic spectral-spatial pulse, where multiple improvements including reduced heating and increased robustness against field imperfections are demonstrated by phantom and in-vivo brain studies at 7T. Second, the use of a variety of radiofrequency management methods with parallel transmission is explored in the human torso for the first time at 10.5T. Preliminary high quality images of multiple anatomies including multi-parametric mappings in the prostate are presented. Last, a novel non-localized efficiency RF shimming is proposed and extended to Acquisition Modes Optimized for Refocused Echoes (AMORE), a novel strategy to design modes in Time Interleaved Acquisition of Modes (TIAMO). Both approaches are optimized for the clinically relevant turbo spin echo imaging while also benefiting other acquisitions. Improvements are demonstrated in vivo and evidenced by a higher transmit efficiency with reduced non-uniformity or signal dropout in multiple targets including brain, knee, and pelvis.Item Assessing the Accuracy and Reliability of Root Crack and Fracture Detection in Teeth Using Sweep Imaging with Fourier Transform (SWIFT) Magnetic Resonance Imaging (MRI)(2017-08) Schuurmans, TylerIntroduction: Magnetic Resonance Imaging (MRI) has the potential to aid in determining the presence and extent of cracks/fractures in teeth due to more advantageous contrast, without ionizing radiation. An MRI technique called Sweep Imaging with Fourier Transform (SWIFT) has overcome many of the inherent difficulties of conventional MRI with detecting fast-relaxing signals from densely mineralized dental tissues. The objectives of this in vitro investigation were to develop MRI criteria for root crack/fracture identification in teeth and to establish intra- and inter-rater reliabilities and corresponding sensitivity and specificity values for the detection of tooth-root cracks/fractures in SWIFT MRI and limited field of view (FOV) CBCT. Materials and Methods: MRI-based criteria for crack/fracture appearance was developed by an MRI physicist and 6 dentists, including 3 endodontists and 1 Oral and Maxillofacial (OMF) radiologist. Twenty-nine human adult teeth previously extracted following clinical diagnosis by a board-certified endodontist of a root crack/fracture were frequency-matched to 29 non-cracked controls. Crack/fracture status confirmation was performed with magnified visual inspection, transillumination and vital staining. Samples were scanned with two 3D imaging modalities: 1) SWIFT MRI (10 teeth/scan) via a custom oral radiofrequency (RF) coil and a 90cm, 4-T magnet; 2) Limited FOV CBCT (1 tooth/scan) via a Carestream (CS) 9000 (Rochester, NY). Following a training period, a blinded 4-member panel (3 endodontists, 1 OMF radiologist) evaluated the images with a proportion randomly re-tested to establish intra-rater reliability. Overall observer agreement was measured using Cohen’s kappa and levels of agreement judged using the criteria of Landis and Koch. Sensitivity and specificity were computed with 95% confidence interval (CI); statistical significance was set at 0.05. Results: MRI-based crack/fracture criteria were defined as 1-2 sharply-delineated, high-signal (bright/white) line shape(s) that must be visible on multiple contiguous image slices. The line shape(s) must present as: single entities, or parallel pairs in close proximity, or pairs in close proximity exhibiting convergence or divergence extending from the external boundary of the tooth to the pulpal cavity. Intra-rater reliability for MRI was fair-to-almost perfect (κ=0.38-1.00) and for CBCT was moderate-to-almost perfect (κ=0.66-1.00). Inter-rater reliability for MRI was fair (κ=0.21; 95%CI:0.10-0.31; p< 0.001) and for CBCT was moderate (κ=0.45; 95%CI:0.34-0.56; p<0.001). Sensitivity: MRI=0.59 (95% CI:0.39-0.76; p=0.46); CBCT=0.59 (95% CI:0.59-0.76; p=0.46). Specificity: MRI=0.83 (95% CI:0.64-0.94; p<0.01); CBCT=0.90 (95% CI:0.73-0.98; p<0.01). Conclusions: Education and training for both imaging modalities is needed to improve reliabilities for the identification of tooth-root crack/fractures. Despite the advantages of increased contrast and absence of artifact from radio-dense materials in MRI, comparable measures of sensitivity and specificity (in relation to CBCT) suggest quality MRI improvements are needed, specifically in image acquisition and post-processing parameters. Given the early stage of technology development and multiple available pathways to optimize MR imaging of teeth, there may be a use for SWIFT MRI in detecting cracks and fractures in teeth.Item Challenges of field inhomogeneities and a method for compensation(2011-11) Styczynski Snyder, Angela LynnMRI of the body at 7 T has become possible only very recently. High fields bring the advantages of increased signal to noise ratio, resolution gains, faster image acquisition through better parallel imaging, improved and novel types of contrast, and greater spectral dispersion. There are many obstacles to be faced in the advancement to 7 T including field inhomogeneities, transmit inhomogeneities, and increased RF-absorption risk. Inhomogeneous B1+ is possibly the most significant obstacle currently facing 7 T body imaging in consistently producing clinical-quality images. In this work, the first demonstrations of MR imaging and spectroscopy (MRS) of the liver at 7 T are presented and evaluated with special attention given to parallel imaging. Also presented here is the first demonstration of imaging of the uterus at 7 T with particular emphasis on contrast between uterine layers. A comparison was done between 3 T and 7 T, and relaxation rates were mapped including higher rotating frame relaxations.SWIRLY (spatiotemporal-encoding with incremental refocusing along a trajectory) is a novel pulse sequence that employs a frequency and amplitude modulated excitation pulse in the presence of sinusoidal gradients to move a region of resonance through space along a spiral trajectory. The signal can be sequentially refocused and acquired in an entirely spatiotemporal manner such that no Fourier Transform is needed for reconstruction. Because each resonance region can be treated entirely independently, this sequence has incredible potential for addressing problems that are inherently spatial in nature, such as B1+ and B0 inhomogeneities.Item A Combined, Fine-Tune B0 Shimming and RF Receive Array using Transmission Line Resonators for Functional Imaging of the Human Temporal Lobe at 7 Tesla(2020-08) Bratch, AlexanderFunctional MRI has become a one of the most powerful tools for non-invasive investigation of brain function. Increases in the magnetic field strength of these systems have yielded improvements in SNR that enable the investigation of fine-scale neural systems. However, with this increase in field strength comes an increase in artifacts arising from magnetic field homogeneity. Specifically, artifacts which occur near air-tissue boundaries (e.g., ear canals and frontal sinuses) become dramatically worse with higher field strengths, limiting the ability to derive useful information from brain areas adjacent to these regions. In recent years, a number of attempts have been made to develop technology which can help mitigate the artifacts arising in these areas. Such approaches make use of either fully external shim arrays, or shimming circuity integrated within standard array technology. Here, the use of transmission line resonators (TLRs) is proposed for use as a combined receive-only/B0 shimming element for imaging and local shimming of the ventral temporal lobe. Simulations were conducted and initial evaluations showed both good bench and in-scanner performance of prototypes. Further design refinements led to the development of an array structure and proposed shimming routine. The resulting TLR coil array structure was integrated into a larger 32 channel RF head array, and associated hardware for selectively driving the shim elements was built. Preliminary results demonstrated strong convergence with simulated shim performance, suggesting the viability of this array design and for the use of TLRs in this application.Item Computer Aided Diagnosis System for Detection of Focal Cortical Dysplasia Lesions on T1 and T2 Weighted MRI(2012-09) Yang, Chin-AnnFocal cortical dysplasia (FCD) is the most frequent malformation for patients with pharmacoresistant epilepsy that require surgical treatment. Providing automated procedures to detect FCD lesions is greatly desirable because visual diagnosis is often challenging, time consuming, and relies highly on the individual's expertise. In this thesis, we propose two Computer Aided Diagnosis (CAD) approaches for Focal Cortical Dysplasia (FCD) lesion detection and segmentation on T1 and T2 weighted MRI. For the rst CAD system, an automatic detection algorithm for FCD lesions on T1 weighted MRI is proposed. Instead of using the traditional voxel-based analysis, we introduce a set of volume-based statistical features with Naive Bayes Classier. Subsequently, a set of cluster-based differential features with a Support Vector Machine (SVM) classier is used to eliminate the false positives (FPs) resulting from the rst processing stage. The advantage of our system lies on the use of volume-based analysis to allow the study of feature distributions in a spatial neighborhood. The second CAD system automatically segments FCD lesions on T2 weighted MRI. We present a Markov Random Field (MRF) model for the segmentation task with a particular emphasis on the incorporation of T1 information with a location prior. By integrating such location prior, we take the advantage of T1 weighted MRI in producing better differentiation of soft tissues into the T2 lesion segmentation task. The proposed algorithms are validated on a dataset that consists a total of 51 subjects with FCD lesions provided by the Radiology Department of Mayo Clinic. The experimental results show a 87% FCD lesion detection rate for T1-weighted MRI and a 100% FCD lesion detection rate for T2 weight MRI. The experimental results also show that proposed methods outperform previous methods in the literature .Item Deep Learning Approaches for Accelerated MRI Reconstruction(2023-05) Zhang, ChiAccelerated MRI is widely used clinically to reduce lengthy scan times, where datasets are sampled in Fourier domain (k-space) below Nyquist rate, and recovered using reconstruction methods that utilize redundancies in datasets or measurement hardware. MRI reconstruction methods either perform interpolation in k-space, or solve an inverse problem with a known forward operator to recover the desired image. Recently, deep learning (DL) has been investigated for both types of MRI reconstruction, with improved image quality at higher acceleration rates. Among k-space interpolation methods, robust artificial-neural-networks for k-space interpolation (RAKI) has been proposed to perform nonlinear k-space interpolation, showing improved noise resilience compared to its linear predecessor (GRAPPA). However, RAKI is time-consuming since it trains multiple convolutional neural networks (CNNs) to reconstruct a single acquisition, and RAKI shows blurring at high acceleration rates, both hindering its applicability in practice. For the inverse problem type methods, physics-guided deep learning (PG-DL) has been shown to offer improved image quality and robustness than purely data-driven approaches. In PG-DL, a regularized inverse problem is solved alternatively between a proximal step solved implicitly by a neural network and a linear data fidelity (DF) step for several unrolled iterations. As a sufficient number of iterations is necessary for both unrolling and internally for DF, PG-DL leads to a deep computational graph that consumes considerable GPU memory during training. Consequently it is challenging to apply PG-DL with several acquisition types, include high-resolution, 3D/4D, and non-Cartesian MRI. Furthermore, for any DL-based approach, recent studies for single-coil datasets suggest they exhibit instabilities against adversarial perturbations, which lead no visible differences at input but impact the reconstruction results. However, the impact of adversarial perturbations against conventional multi-coil MRI remains uninvestigated, which is the more clinically used acquisition setup. This thesis studies DL-based approaches for MRI reconstruction in terms of their practical translation. First, we investigate scan-specific DL methods, starting with strategies to reduce the processing time of RAKI from hours to a clinically acceptable range within seconds. This is achieved by utilizing multi-processing and a novel line-by-line network architecture which reduces the number of CNNs trained during reconstruction. We further propose residual RAKI (rRAKI) that performs hybrid linear and nonlinear k-space interpolation, where a linear convolution provides baseline reconstruction jointly with a nonlinear component for noise and artifact reduction. Compared to linear methods, rRAKI exhibits improved noise resilience, similar to RAKI, while rRAKI offers improved image sharpness compared to RAKI. We then move to database DL approaches, focusing on PG-DL. In this setting, we tackle the memory consumption issues for large-scale PG-DL. By combining several memory-efficient techniques, PG-DL of 3D, high-resolution, multi-coil, non-Cartesian MRI is achieved. These techniques include check-pointing that keeps only one unrolled step on GPU; a Toeplitz characterization for non-Cartesian encoding and decoding operations that replace memory consuming convolutional operations with point-wise multiplications; distributed learning techniques that exploit linearity of multi-coil DF terms to distribute it into multiple GPUs; and mixed precision training that trains image-domain CNN via half-precision, and DF that works with k-space data in single precision. We then propose a 2.5D PG-DL for 3D reconstruction to tackle the issue of insufficient training data in these 3D non-Cartesian applications. The 2.5D PG-DL consists of three 2D CNNs that treat 3D volumes as batches of 2D images from three orthogonal views, such that the 2D CNNs have access to a sufficient number of 2D images from limited 3D volumes during the training. The 3D reconstruction is formulated using three constraints over 2D views and finally unrolled via variable splitting with quadratic penalty. Our results suggest that the proposed 2.5D PG-DL offer improved image sharpness compared to conventional 3D PG-DL for limited training data. Finally, we investigate the impact of adversarial attacks on conventional multi-coil MRI techniques including SENSE, GRAPPA and compressed sensing. Our results show that adversarial perturbations generated on the zero-filled image, with constraints on its l∞ norm, impact all conventional multi-coil MRI techniques, leading to substantial degradation in reconstruction at high acceleration rates. Our results also suggest that the main cause of failure in PG-DL methods against adversarial attack is the linear DF step rather than the nonlinear regularizer.Item Determining optimum imaging parameters for SWIFT: application to superparamagnetic iron oxides and magnetized objects.(2011-06) O’Connell, Robert DanielA relatively new pulse sequence in MRI known as SWIFT, sweep imaging with Fourier transformation, has been shown to effectively image spins with both short and long transverse and longitudinal relaxation rates. It is desirable to have equations that accurately describe the signal of spins when excited by SWIFT; however the Bloch equations are not easily solvable for the SWIFT sequence for all relaxation rates and flip angles. The purpose of this work is to determine a set of optimization equations for the SWIFT sequence through comparison to the Ernst energy equations via a Bloch simulator. An innovative contrast technique is also developed. The optimization equations are then tested experimentally and applied to imaging of superparamagnetic iron oxides. Susceptibility artifacts distort images around metal objects. In SWIFT images the susceptibility artifacts manifest as signal voids surrounded by pileup artifacts. This work develops predictive equations for the pileup artifacts around metallic spheres. A technique called ROC, radial off-resonance correction, is developed to reconstruct distorted images by utilizing the pileup predictive equations in post-processing.Item Developing interactions between executive function and emotion during adolescence.(2010-10) Cohen, Julia E.Adolescence is reputed to be a time of heightened emotionality and limited impulse control. Furthermore, emotion is frequently cited as the instigator of impulsive actions within this developmental period. That is, adolescents' powerful emotions may disrupt efforts to self-regulate and lead to impulsive actions that do not, in fact, serve the individual's long-term goals. Additionally, poor decision-making during this age range frequently has serious negative consequences. Understanding the cognitive and neurobiological mechanisms underlying the developing relationship between emotion and cognitive control may ultimately help us encourage teens to avoid potentially dangerous decisions and actions. To this end, this dissertation presents four studies aimed at better understanding the influence of emotion on higher-level cognition and self-regulation during adolescence. The first study introduces a task that requires participants to ignore emotional images while exercising inhibitory motor control (a go-nogo task). The second study uses functional magnetic resonance imaging (fMRI) to explore age differences in brain activation during performance of the emotional-distraction go-nogo task introduced in the first study. The third study extends the emotional distraction paradigm to a second form of higher-level cognition by using emotional images as backgrounds in an n-back working memory task. The fourth study examines the influence of early institutional care and BDNF genotype on performance of the emotional-distraction go-nogo task. Together these studies inform us regarding developmental changes in the interface between emotion and cognition during adolescence.Item Development and Validation of a Multinuclear Magnetic Resonance Spectroscopy Toolkit for Bioartificial Pancreas Assessment(2016-06) Einstein, SamuelType 1 diabetes is a devastating disease with increasing incidence and prevalence. Insulin therapy, while life-saving, does not prevent severe complications that substantially increase both morbidity and mortality. Whole pancreas and pancreatic islet transplantation are treatments for diabetes, but favorable long-term outcomes are inconsistent and the procedures are restricted to a small group of patients due to a variety of limitations. These impediments include the current demand for donor pancreata far exceeding supply, allotransplantation requiring a lifetime of immunosuppression, and premature graft failure. Macroencapsulated tissue-engineered grafts (TEGs) may mitigate or eliminate these limitations by allowing the use of alternative cell sources (such as porcine or stem-cell-derived islets), providing immunoisolation, and encourage graft survival through therapeutic interventions. TEGs possess great potential, but require significant development to fulfill their promise of a safe, effective, and definitive cure for type 1 diabetes. To enable and expedite TEG development, novel techniques to assess oxygen status (pO₂) and viability were developed, validated, and applied. Hypoxia is currently the most significant obstruction preventing widespread utilization of TEGs, rendering measurements of TEG pO₂ critically necessary. Fluorine-19 magnetic resonance spectroscopy (¹⁹F-MRS) was adapted for in vivo pO₂ measurement in TEGs and validated with a well-established technique. It was found that ¹⁹F-MRS can be a robust, accurate, and noninvasive technique to monitor TEG pO₂ for long durations post-implantation. This technique was applied to the murine model and demonstrated that TEGs implanted subcutaneously experience hypoxia unconducive to supporting islet viability and function. Therefore, a method for the delivery of supplemental oxygen (DSO) to increase in vivo pO₂ was developed and its efficacy was evaluated with ¹⁹F-MRS. It was found that DSO can successfully increase the pO₂ of macroencapsulated TEGs and enhance islet survival. While providing crucial information, measuring pO₂ does not necessarily correlate to islet viability, necessitating the development of additional techniques. Islet viability was first assessed by measuring pO₂ with ¹⁹F-MRS and calculating the oxygen consumption rate (OCR) using a mathematical model. Finally, to facilitate in vivo viability assessment and increase measurement accuracy, oxygen-17 MRS was developed to directly measure and noninvasively quantify the OCR of TEGs.Item Development Of Multi-Modal Techniques For The Investigation Of Brain Energetics(2015-10) Taylor, JenniferThe study of spontaneous and highly variable brain activity, or task-evoked activity and its quantitative relationship with neuroimaging signals, is severely restricted by the lack of techniques to investigate multiple measures of brain activity simultaneously. In order to study the coupling and interactions between metabolic, hemodynamic, and neuronal activity, we here develop the technology to acquire in vivo magnetic resonance (MR) spectroscopy (MRS) simultaneously from two or more nuclei, as well as develop MR-compatible electrodes for neuronal recording in the MR scanner with minimal susceptibility artifacts. We apply these techniques to investigate metabolic trends resulting from a whole brain occlusion in the rat and to study neuronal, hemodynamic, and network responses to changes in anesthesia depth. Lastly, we show the first steps in developing an MR-compatible optrode to allow simultaneous MR imaging (MRI), neuronal recording, and optogenetic stimulation. With these new techniques, a wide field of studies becomes feasible to investigate direct neuronal, metabolic, and hemodynamic correlations under resting and working conditions to advance our understanding of brain function and dysfunction.Item Fluorinated Metal Complexes as MRI Contrast Agents(2015-08) Weitz, EvanMagnetic resonance imaging (MRI) is a vital tool in today’s modern healthcare system. MRI is preferred over positron emission tomography (PET) and X-ray computed tomography (CT) because it is non-invasive, non-radioactive, and provides 3-D imaging directly in vivo. Contrast agents are used in order to enhance the resolution of the images from MRI. All currently used contrast agents are based on gadolinium and image water protons in the human body. However, gadolinium-based contrast agents are principally unable to quantitatively image specific biomarkers of diseased states, lacking a ratiometric mechanism. Fluorine-based MRI does not suffer from these limitations, but its low sensitivity, with a limit of detection (LOD) in the micromolar range first requires a contrast agent designed specifically to address this issue of sensitivity, which can be accomplished using contrast agents with an incorporated lanthanide center. Fluorine MRI eliminates background signals and has a large chemical shift range which enables fluorines in different environments to each be imaged independently. This in turn allows for the development of ratiometric, responsive contrast agents whereby the total probe concentration and the concentration of the analyte can be independently determined. In this thesis, the theory, practicality, utility, and potential for fluorine-based MRI contrast agents is described. Sensitivity is addressed, synthesis is described, and demonstrations of the potential for fluorine MRI are examined in vitro and in vivo in order to design highly-sensitive, responsive, and biocompatible fluorine contrast agents.Item Heritability of Behavioral and Brain Measures in a Large Cohort of Healthy Twin and non-Twin Subjects(2020-01) Joseph, JasmineThis research investigated comprehensively the effects of genetics on behavioral traits, brain structure and function, and their associations in a large cohort of monozygotic (MZ) twins, dizygotic (DZ) twins, non-twin siblings (SIB) and non related (NR) individuals (N = 1206, total) provided by the Human Connectome Project (HCP). All primary measures available are of the highest quality and quantitatively assessed. They include the following for each individual: (a) Measures of behavioral traits in 5 domains (motor, sensory, cognitive, emotion, and personality); (b) volumes of 70 cortical brain areas extracted from high-resolution (0.7 mm isotropic) structural magnetic resonance imaging (sMRI) data; (c) resting-state blood oxygenation level dependent (BOLD) activity of the same areas extracted from long-duration (1200 volumes), fast-acquisition (every 0.72 s), high-resolution (2 mm isotropic) functional MRI (fMRI) data; and (d) white matter integrity measures (fractional anisotropy [FA] and mean diffusivity [MD] for 7 brain regions regions) derived from high angular resolution diffusion imaging (HARDI) MRI (dMRI) data at 1.25 mm spatial resolution and very strong magnetic field gradients at (100 mT/m). Data extraction and preprocessing was performed using a dedicated 704-processor high-performance computer cluster at the Brain Sciences Center using Matlab. Univariate and multivariate statistical analyses were carried out in personal computers using Matlab and IBM-SPSS (version 24). These analyses include the following. (a) Computation of common univariate statistics (mean, variance, etc.); (b) computation of intra class correlation (ICC) for each of the 4 genetic groups (MZ, DZ, SIB, NR) and its z-transform [zICC = atanh(ICC)] for each primary measure above; (c) analysis of variance (ANOVA) of zICC across genetic groups for each measure; (d) computation of heritability using Falconer’s formula; (e) multidimensional scaling (MDS) and hierarchical tree clustering (HTC) of this heritability for the different data sets (behavioral, sMRI, fMRI, dMRI). These analyses yielded substantial new information on the effects of genetics on brain and behavior, and partially elucidated underlying associations among the various diverse measures above. To our knowledge, this is the first such comprehensive study carried out.Item High-Resolution Breast Diffusion Weighted Imaging with Improved Nyquist Ghost Correction and Simultaneous Multislice Imaging(2020-07) McKay, JessicaDiffusion-weighted imaging (DWI) is a quantitative MRI method that measures the apparent diffusion coefficient (ADC) of water molecules, which reflects cell density and serves as an indication of malignancy. Unfortunately, however, the clinical value of DWI is severely limited by the undesirable features in images that common clinical methods produce, including large geometric distortions, ghosting and chemical shift artifacts, and insufficient spatial resolution. Thus, in order to exploit information encoded in diffusion characteristics and fully assess the clinical value of ADC measurements, it is first imperative to achieve technical advancements of DWI. The purpose of this work is to improve DWI methods for breast imaging at 3 Tesla to robustly provide diffusion-weighted images and ADC maps with anatomical quality and resolution. This dissertation will first lay out the background information to provide clinical motivation for this work and explain the current standard in breast DWI, as well as some alternatives proposed throughout the literature. The main work of this project has two major parts: Nyquist ghost correction and the use of simultaneous multislice imaging (SMS) to achieve high resolution. Exploratory work was completed to characterize the Nyquist ghost in breast DWI, showing that, although the ghost is mostly linear, the three-line navigator is unreliable, especially in the presence of fat. A novel referenceless ghost correction, Ghost/Object minimization was developed that reduced the ghost in standard SE-EPI and advanced SMS. An advanced SMS method with axial reformatting (AR) is presented for high resolution breast DWI. In a reader study, AR-SMS was preferred by three breast radiologists compared to the standard SE-EPI and readout-segmented-EPI. Finally, future directions are suggested, including some preliminary work explored throughout this project.Item Investigation of intravenous administration of non-hematopoietic umbilical cord blood cells as a therapy for stroke(2013-05) Juliano, MarioStroke is one of the leading causes of death in the United States. Limitations of currently available stroke treatment include a 3 hour time window for recombinant tissue plasminogen activator. Stem cells have become promising for the treatment of a variety of neurodegenerative diseases, including stroke. Therapies in this category include stimulation of endogenous neurogenesis, as well as the delivery of exogenous stem cells.This thesis focuses on the investigation of the intravenous delivery of a CD34 negative subset of umbilical cord blood stem cells as a therapy for stroke. Methods employed for this investigation include next generation sequencing technologies for gene expression profiling, 19-fluorine tracking of stem cells with MRI, and fluorescence biodistribution tracking.Item Magnetic Nanowires for MRI Contrast, Cell Separation, Remote Magnetic Heating, and Collagen Hydrogels(2018-07) Shore, DanielMagnetic nanoparticles of various shapes, sizes and compositions have proven useful tools for nanomedicine in recent years. Magnetic nanowires (NWs) fabricated by template electrodeposition have tunable diameters (tens to hundreds of nm) and lengths (nm to tens of microns). High magnetization metals and alloys, such as Ni, Co, Fe, and CoFe, can be electrodeposited; multiple layers of non-magnetic metals, such as Au or Cu, can be added to make multilayer NWs. Because of their high aspect ratios, the NWs have a large surface area, with inherent shape and magnetic anisotropy, so they are easy to manipulate or align by an external magnetic field. Each of these factors gives NWs an advantage over isotropic magnetic nanoparticles, for certain applications. In addition, the surface of the NWs may be functionalized for biocompatibility or to target specific biological applications. This thesis investigates using magnetic NWs for magnetic resonance imaging (MRI) contrast, remote heating by magnetic hysteresis, cell separation with external fields, and aligning collagen hydrogels with an external field. This research has analyzed important engineering questions regarding the design and synthesis of the NWs, including shape, size, composition, magnetic properties, surface functionalization, and nanoparticle aggregation. The NWs were compared against the current state-of-art nanoparticles for these applications, to demonstrate feasibility, highlight successes, analyze drawbacks, and discuss a path forward for improvement and implementation.Item MicroRNA and Neuroimaging Biomarkers of Neuropathic Pain Severity After Spinal Cord Injury: Results from a Robotic-Assisted Gait Training Study(2022-07) Kowalski, JesseSpinal cord injury (SCI) results in chronic neuroinflammation which contributes to altered neural function and the development of neuropathic pain. Differential expression of microRNA regulators of neuroinflammatory pathways and alterations in brain structure and functional connectivity may contribute to the development or severity of neuropathic pain. Exercise has been shown to reduce neuroinflammation and chronic pain and alter brain structure in human and animal models, yet little is known about how exercise interventions influence pain processing in human populations with SCI. This doctoral dissertation aimed to identify 1) novel microRNA biomarkers of neuropathic pain, 2) neuropathic pain-related alterations in brain functional connectivity, and 3) the efficacy of an exercise intervention of robotic-assisted gait training to reduce neuropathic pain and alter brain volume in individuals with SCI. Successful identification of underlying mechanisms of neuropathic pain and potential exercise induced mitigation of these factors will guide the development of targeted interventions and provide useful biomarkers to predict and optimize prognosis, and subsequent care management for individuals with SCI.Item Monitoring and improving oxygenation of organs, cells, and tissue engineered grafts(2015-12) Weegman, BradleyOxygen is vital to the survival of many living things, and evolution has provided the human body with a complex cardiovascular system to ensure that all of the cells in the body are provided with adequate oxygen. Achieving adequate oxygen delivery remains of critical importance to the clinical management of many human diseases and has been the impetus for the development of many medical procedures and technologies. Despite much advancement in the understanding about oxygen delivery in the body, the current inability to attain life-sustaining levels of tissue oxygenation remains the major limitation for the emerging fields of cell, tissue, and organ replacement. There is a large body of research focused on developing methods to improve vascularization and oxygen supply for transplanted cells, tissues and organs, and this substantial challenge will require an interdisciplinary approach utilizing both engineering principles and a broad understanding of the physical science. The islet transplantation process can be divided into three critical steps: tissue procurement and preservation; isolation, culture and shipment; and graft transplantation and monitoring. To begin, whole organ oxygen consumption rate (WOOCR) measurements are presented for the assessment of organ viability, followed by the description of new techniques for improving the efficacy of pancreas cooling during procurement, and the use of hypothermic machine perfusion (HMP) to improve pancreas preservation. These methods can be used to qualify biological tissue products and to evaluate and improve organ procurement and preservation. Next, HMP combined with silicon-rubber-membrane (SRM) culture systems are presented as techniques to improve the quality of tissues isolated from juvenile porcine pancreata, and advanced nutrient supplementation with suspension culture systems are shown to improve β-cell expansion. Finally, 19F-MRS oximetry techniques are presented for non-invasive oxygen monitoring of tissue-engineered grafts (TEGs), and these techniques are further applied to develop, implement, and validate a novel method for oxygen delivery to an implanted tissue-engineered islet grafts.