Doctor of Philosophy, Case Western Reserve University, 2024, EECS - Electrical Engineering

Quantitative Magnetic Resonance Imaging (qMRI) is a powerful tool for detecting biochemical abnormalities without harmful ionizing radiation and invasive procedure, which can significantly enhance early disease diagnosis and progression monitoring compared to standard morphological MRI. Osteoarthritis is a disease significantly impacting joint function, mobility, and quality of life, often leading to chronic pain and reduced physical activity. Despite the significant impact, the disease lacks sensitive biomarker that can detect and track the disease progression from an early stage which can help improve patient outcomes and develop effective treatment for the disease. qMRI, due to its sensitivity to biochemical properties, provide multiple candidates that may serve as imaging biomarkers for OA. Among them, T2 and T1ρ have advantage of not requiring special coil nor contrast agent. However, challenges need to be addressed to expand the accessibility of the technique and successful translation to be used in large scale clinical trials and in clinical practice. In this study, novel quantitative T2 and T1ρ acquisition techniques were developed to enhance reliability and enable faster acquisition.

Committee: Xiaojuan Li (Advisor); Mark Griswold (Committee Member); Xin Yu (Committee Member); Cenk Cavusoglu (Committee Chair) Subjects: Biomedical Engineering; Electrical Engineering

Master of Sciences, Case Western Reserve University, 2023, Applied Anatomy

The sympathetic nervous system, a subdivision of the autonomic nervous system, innervates glands, smooth and cardiac muscle of the body and drives the “fight or flight” response. The objective of this study is to use anatomical and radiological methods to definitively identify and investigate the sympathetic chain, specifically ganglia from stellate through T5. The overarching goal of this research is to help guide clinical treatments, including nerve block and ligation procedures, for various disorders of the sympathetic nervous system, including cardiac arrhythmias, hyperhidrosis and pain syndromes. This study uses anatomical methods, including cadaveric dissection, optical tracking, anatomic relationships and landmarks, to investigate the characteristics of the sympathetic chain. This study also uses radiologic methods, including conventional radiography and 3 Tesla (T) magnetic resonance imaging (MRI) with a high-resolution 3D constructive interference in steady state (CISS) sequence, to provide a clinically applicable comparison to gross anatomic observations and measurements.

Committee: Andrew Crofton (Committee Co-Chair); Ari Blitz (Committee Co-Chair); Darin Croft (Committee Member) Subjects: Anatomy and Physiology; Biology; Health; Health Sciences; Medical Imaging; Medicine; Neurobiology; Neurology; Neurosciences; Radiology

Doctor of Philosophy, Case Western Reserve University, 2017, Biomedical Engineering

Quantification of tissue properties has long been a research goal in Magnetic Resonance Imaging (MRI). However, the long acquisition time of the conventional quantitative method prohibited its adoption in the clinic. The recently proposed Magnetic Resonance Fingerprinting (MRF) is a novel framework that simultaneously quantifies multiple tissue properties using pseudorandom acquisition parameters. It breaks the convention of MRI which acquires a steady- state signal with fixed acquisition parameters, and thus MRF can exploit all degrees of freedom in the pulse sequence design. With nearly unlimited choices of sequence parameters, the thesis explored and presented MRF methods based on the QUick Echo Split NMR technique (QUEST) to reduce the Specific Absorption Rate (SAR), the Fast Imaging with Steady-state Precession (FISP) to improve the performance with off-resonance, the Double Echo Steady-state (DESS) to quantify diffusion, and a Simultaneous MultiSlice (SMS) MRF to further reduce the acquisition time. The development of these novel methods improves the robustness of MRF and have the potential to extend MRF to wide ranges of applications.

Committee: Mark Griswold PhD (Advisor); Nicole Seiberlich PhD (Committee Chair); Xin Yu PhD (Committee Member); Erkki Somersalo PhD (Committee Member); Jeffrey Sunshine MD,PhD (Committee Member) Subjects: Biomedical Engineering

Doctor of Philosophy, The Ohio State University, 2015, Biomedical Engineering

An acute coronary syndrome (ACS) is a life-threatening event in the heart which affects over one million Americans each year. Although not currently part of the standard of care for ACS, magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques may be able to improve outcomes in patients with ACS. The majority of ACS cases are classified, using electrocardiogram (ECG), as non-ST segment acute coronary syndrome (NSTE-ACS). Diagnosis, risk assessment, and selection of management strategy can be difficult in this syndrome. A novel large animal model was created for study of NSTE-ACS by combining a partial coronary artery stenosis with ventricular pacing. In this animal model, MRI images of the heart were acquired, as well as oxygen respiration rates in myocardial tissue, troponin levels, and histology samples. T2 MRI, a technique which identifies myocardial regions with altered chemistry, was found to be elevated in ischemic myocardium. These T2 changes corresponded to reduced myocardial tissue respiratory function. Reperfusion reversed both T2 elevation and tissue respiratory depression, indicating that the early myocardial changes causing acute T2 elevation are reversible. This important property of T2 was supported by ultrastructural findings indicating myocardial viability and by the lack of late gadolinium enhancement (LGE) positivity or high troponins, which are tests to identify the presence of necrosed myocardium. An elevated T2 value thus may be a highly informative marker of acute reversible myocardial injury in NSTE-ACS and may reflect cellular changes (including respiratory function) which are not detectable by other tests or modalities yet have important implications on clinical decisions for patient management. Reversibly injured myocardium (identified by elevated T2) represents a target for reperfusion strategies that can prevent the progression to myocyte death and restore normal myocardial functionality. After an ACS, all patien (open full item for complete abstract)

Committee: Subha Raman MD (Advisor); Orlando Simonetti PhD (Committee Member); Elliott Crouser MD (Committee Member); Stephen Lee PhD (Committee Member) Subjects: Biomedical Engineering; Biomedical Research; Medical Imaging; Medicine

Doctor of Philosophy, University of Akron, 2015, Chemistry

Multiple systems were studied to advance the understanding of the chemical composition of the materials. These materials contained various structures or structures within different physical phases. Solid-state NMR techniques were used to probe effects of different chemical processes and environmental conditions on the chemical structures and phase composition of these materials. Much of the high thermal and chemical resistance of poly(vinylidene-co-hexafluoropropylene) is gained from cross-linking. The insolubility of the cross-linked fluoroelastomer has prevented the characterization of the structure at the cross-link site by NMR. Samples from each of the four stages of the cross-linking of poly(vinylidene-co-hexafluoropropylene) were analyzed with solid-state NMR to determine the chemical structure at the cross-linking site and the effects of cross-linking on the mobility of the elastomer chains. Spectral overlap from chemical shift dispersion hindered the use of simple 1D techniques to assign structural components to peaks in the NMR spectra. Relaxation studies that measured T1, T2, and T1ρ relaxation times were used to assign new peaks in the NMR spectra to the fluoride salts that are produced during cross-linking. The NMR relaxation data also indicated no reduction in the mobility of the fluoroelastomer from cross-linking. The chemical structure of the cross-link site was partially characterized by 2D-NMR. However, the amorphous nature of the polymer inhibited a full characterization of this location with 2D-NMR techniques. The structures that were identified at the cross-link site supported proposed structures. Solutions of NaCl and dextrose used in the preservation of premixed drugs were analyzed to distinguish the solid and liquid phases over a temperature range of -60 to 20 °C. The large chemical shift dispersion in the NMR spectra made analysis of the frequency domain data difficult. The time domain data of the single pulse NMR experiments were analyzed (open full item for complete abstract)

Committee: Peter Rinaldi Dr. (Advisor); Chrys Wesdemiotis Dr. (Committee Member); David Modarelli Dr. (Committee Member); Leah Shriver Dr. (Committee Member); Elizabeth McCord Dr. (Committee Member); Toshikazu Miyoshi Dr. (Committee Member) Subjects: Analytical Chemistry; Chemistry

Doctor of Philosophy, Case Western Reserve University, 2015, Biomedical Engineering

Magnetic Resonance (MR) is an exceptionally powerful and versatile measurement technique. The basic structure of an MR experiment has remained nearly constant for almost 50 years. Here we introduce a novel paradigm, Magnetic Resonance Fingerprinting (MRF) that permits the non-invasive quantification of multiple important properties of a material or tissue simultaneously through a new approach to data acquisition and post-processing. MRF provides a new mechanism to quantitatively detect and analyze complex changes that can represent physical alterations of a substance or early indicators of disease. MRF can also be used to specifically identify the presence of a target material or tissue, which will increase the sensitivity, specificity, and speed of an MR study, and potentially lead to new diagnostic testing methodologies. Because of its basis in pattern recognition, MRF inherently suppresses measurement errors and thus can improve accuracy and efficiency compared to previous approaches. By taking the advantage of the extra degrees of freedom of the MRF concept, the MRF-Music sequence is presented as a special form of the MRF to improve the patients' comfort level during the MR scans while still maintaining a high image quality and scan efficiency.

Committee: Mark Griswold (Advisor); Nicole Seiberlich (Committee Chair); Vikas Gulani (Committee Member); David Wilson (Committee Member); Jeffrey Duerk (Committee Member); Daniela Calvetti (Committee Member) Subjects: Biomedical Engineering

Doctor of Engineering, Cleveland State University, 2009, Fenn College of Engineering

Novel tyramine-based hyaluronan (HA) and collagen hydrogels have been developed in which cross-linking is accomplished via peroxidase-mediated dityramine linkages allowing direct cross-linking in vivo. These TB hydrogels possess advantageous physical properties, which include excellent biocompatibility and the ability to mimic the biological, structural and mechanical properties of normal, healthy tissues, including cartilage, and thus provide for synthetic, implantable biomaterials suitable for a wide range of tissue types. The efficacy of these TB-hydrogels has been previously tested in a number of clinically relevant animal models, which have evaluated their applicability for the repair/replacement of various tissues, including cartilage. Nevertheless, there exists a fundamental need for non-destructive methods to identify, distinguish, quantify and trace these biomaterials in vivo. Magnetic Resonance Imaging (MRI) is a broadly used non-invasive clinical imaging methodology that allows direct visualization of soft tissues. Our results indicated that T1 and T2 mapping can differentiate and measure changes in HA and collagen concentration both alone and in combination with composite materials, composed of HA and collagen at the concentrations found in cartilage resulting in T1 values representative of cartilage. Furthermore, the dGEMRIC technique was able to quantify the HA concentration in phantoms of known HA concentration. These MRI techniques could detect and differentiate the tyramine-based hydrogels in implanted joints, and accurately quantify their volumes.

Committee: Anthony Calabro PhD (Committee Chair); Nolan Holland PhD (Committee Co-Chair); Lars Gilbertson PhD (Committee Member); Mark Kayanja MD, PhD (Committee Member); Miron Kaufman PhD (Committee Member) Subjects: Biomedical Research; Materials Science; Polymers

Doctor of Philosophy, Case Western Reserve University, 2009, Biomedical Engineering

MRI provides different types of exquisite soft tissue and functional contrast. However, depending on the desired contrast and spatial resolution properties, the acquisition time can be quite long. The long-term objective of this work is to improve methods to quickly and accurately diagnose human disease using MRI and provide resources that can be used for image-guided therapy and real-time imaging.Balanced steady state free precession (bSSFP) or True-FISP provides the highest signal-to-noise ratio efficiency of any pulse sequence. However, in bSSFP, contrast is a mixture of T1 and T2 weightings, which is often not desired clinically, and the signal from flowing blood is hyperintense, which can obscure the vessel wall and create artifacts. Also, there are obstructive saturation band artifacts at intersections of rapidly-acquired multiplanar images. The objective of this work was to modify the magnetization preparation and readout properties of the bSSFP sequence to: 1) improve methods that eliminate T1 and isolate T2 contrast, 2) suppress the signal from flowing blood, and 3) characterize and reduce the saturation banding artifacts. A new T-One insensitive Steady State Imaging (TOSSI)-bSSFP combined acquisition technique, Resolution Enhanced TOSSI (RE-TOSSI), has been developed by using a partial Fourier acquisition and eliminating the inversion pulses from TOSSI after the data around the center of k-space is acquired. Results show that TOSSI contrast is maintained, while spatial resolution degradation is reduced. Additional benefits include reduced RF power deposition and faster imaging time. Application to high-resolution, non-subtraction thermal ablation monitoring is demonstrated. An improved dark blood bSSFP pulse sequence (HEFEWEIZEN) has been developed by introducing spatial saturation in True-FISP. This method does not increase the repetition time (TR) or substantially alter stationary tissue contrast and allows for directional suppression of blood flow (e.g. (open full item for complete abstract)

Committee: Jeffrey Duerk PhD (Advisor); Mark Griswold PhD (Committee Member); Roger Marchant PhD (Committee Member); Jeffrey Sunshine MD/PhD (Committee Member) Subjects: Biomedical Research; Engineering; Health Care; Physics; Radiology; Scientific Imaging; Surgery

Master of Sciences (Engineering), Case Western Reserve University, 2008, Biomedical Engineering

Atherosclerotic vulnerable plaque imaging is an important clinical goal. Cryo-imaging can validate vessel tissue classification. A validation study showed overall sensitivity of 89% using naive raters. However, cryo-imaging cannot be clinically translated. Instead, MRI microcoil imaging shows promise. An important component of MR tissue identification is parameter estimation of T1, T2, and proton density. A new parameter estimation method based on Maximum Likelihood Estimation accounting for Rician noise bias with Markov Random Field spatial regularization was developed. A flat image test case shows decreased noise levels comparable to neighborhood averaging. For the lowest signal-to-noise ratio test case, neighborhood averaging decreased the standard deviation of the error to 34% of the single-pixel techniques, while the new method decreased it 37-43%. Tests using simulated phantom image also show well-preserved edges, which is not possible with neighborhood averaging. Finally, the algorithm was tested on brain data to fit T2*, showing visually positive results.

Committee: David Wilson (Advisor); Mark Pagel (Committee Member); Jeff Duerk (Committee Member) Subjects: Biomedical Research; Engineering; Radiology