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Access Type
WSU Access
Date of Award
January 2024
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Chemistry
First Advisor
Eduard Y. Chekmenev
Abstract
The human respiratory system has been one of the focal points in medical research, driven by a need to better understand the dynamics and function of the lung, including gas ventilation, alveolar viability, gas-exchange efficiency, etc. This focus is motivated by the need of early pulmonary disease detection, precise treatment planning, effectively monitoring disease progression, and treatment efficacy. The urgency of this endeavor was further underscored in 2019 with the emergence of global pandemic of SARS-CoV-2 (COVID-19), as COVID-19 adds significantly extensive complications to the lung health compared to any other human organ.1-3 In addition to COVID-19, other lung-related diseases, e.g., Chronic obstructive pulmonary disease (COPD),4-7 lower respiratory infections,8 trachea, bronchus,9, 10 are responsible for almost 7.7 million deaths annually, and affects the lives of hundreds of millions of others every year.11 Over 545 million individuals worldwide are currently living with chronic respiratory conditions, which represents 7.4% of the global population.4 Cumulatively, this highlights chronic respiratory conditions as one of the biggest health concerns around the globe and therefore, better diagnosis of lung functionality in these disease states is desperately needed.Detection and understanding of various physiological processes and diseases in the human body, e.g., brain, heart, injuries to the liver, and cancer development, can be investigated using bio-medical sensing techniques, e.g., Magnetic Resonance Imaging (MRI), Computed Tomography (CT) and Positron Emission Tomography (PET). Radiation generated from CT scans and X-rays has an adverse effect on the human body and can stimulate cancer ceFll division if applied to any stage of cancer and associated with the risk of DNA damage. Detecting discrepancies and abnormalities in the water-rich soft tissues is safer using MRI due to the absence of ionizing radiation. Standard clinical MRI technique uses external radio frequency (RF) pulses and magnetic fields to detect thermally polarized protons to generate images. Moreover, MRI has much better contrast in soft tissue that provides excellent images.12-20 However, even with the MRI technique, a satisfactory detection of lung functionality is challenging to date. Conventional proton MRI of the brain and other body parts is established in routine clinical practice because conventional MRI uses protons of the body's water molecules to generate signals. Our body contains a substantial amount of protons; thus, a clear signal (image) originating from abundant protons of fat and water, can be produced, even at thermal equilibrium.21 However, the lungs possess low proton densities (estimated one-third of muscle).22 As a result, proton MRI of the lung with high-resolution has been challenging. With advanced conventional MRI and CT method, it is possible to get detailed anatomical images of lung structural morphology, but high-resolution imaging and detection of disorder in the lungs using these approaches is far from the standard needed for medical diagnosis. However, utilizing an inhalable gas that does not induce any acute side effects and provides a detectable signal, has the potential to resolve the challenges associated with lung MRI.23 Studies to this effect have been demonstrated using thermally polarized inhalable perfluorinated gas (fluorine-19), which is non-toxic, abundant and has no background signal while detection, thereby makes it ideal for lung imaging. However, these approaches require a long scan time due to signal averaging and relatively low resolution, which are significant drawbacks for this method.24-26 The shortcoming of sensitivity related to perfluorinated gas can be resolved by using hyperpolarized gas (HP). Hyperpolarization is a technique where the nuclear spin of a material is polarized in the presence of an external magnetic field, far beyond the thermal equilibrium level.23 HP NMR active gases (e.g., 3He, 13C, 129Xe, etc.) have the potential to be used as an MRI contrast agent within the lungs by imaging the gas as it permeates the airways upon inhalation. HP noble gases (e.g., 3He, 129Xe etc.) have a good signal-to-noise ratio (SNR); they are non-toxic, can stay hyperpolarized in an external magnetic field (B0) for an extended period, typically in the range of 150-200 minutes.27 However, the production of HP noble gases is associated with high cost of instrumentation, and lengthy HP gas production time. In contrast, the production of HP gases such as propane and butane are more cost-effective and less time-consuming, however they cannot stay hyperpolarized for long, typically at a range of 2-5 seconds, in-vitro.28-32 There are many hyperpolarization techniques developed over the years, such as dynamic nuclear polarization (DNP),33 spin exchange optical pumping (SEOP),34, 35 parahydrogen-induced polarization (PHIP),36 and signal amplification by reversible exchange (SABRE).37 Among these techniques, my research focuses on SEOP, PHIP and SABRE. In this dissertation, I explore the use of HP 129Xe gas produced using the SEOP process as an MRI contrast agent for functional pulmonary imaging. My research includes a comprehensive investigation of instrumentation, production optimization, and pilot quality-assurance of a clinical-scale batch-mode generation-3 (GEN-3) hyperpolarizer for robust production of HP 129Xe gas. Moreover, I will discuss the MR imaging of the ejected HP 129Xe gas produced by using the GEN-3 hyperpolarizer in a 0.35 T clinical MRI scanner. Additionally, I present 0.35 T MRI studies of HP butane and propane gas produced by PHIP hyperpolarization technique in Tedlar bags and excised rabbit lungs. The study helps to establish these HP gases as a potential HP contrast agent in MRI, bridging the gap between fundamental research and clinical practice. Finally, I will present on the development of a purpose-built NMR spectrometer that was developed for ultra-low-field NMR spectroscopy (2 - 125 kHz), and it was utilized to study SEOP and SABRE hyperpolarization processes, and to perform NMR polarimetry.
Recommended Citation
Chowdhury, Md Raduanul, "Clinical-Scale Hyperpolarizers For Low-Field Pulmonary Mri: Development, Optimization, And Validation" (2024). Wayne State University Dissertations. 4051.
https://digitalcommons.wayne.edu/oa_dissertations/4051