Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Parraga, Grace E.

Abstract

Gas-exchange is the primary function of the lungs and involves removing carbon dioxide from the body and exchanging it within the alveoli for inhaled oxygen. Several different pulmonary, cardiac and cardiovascular abnormalities have negative effects on pulmonary gas-exchange. Unfortunately, clinical tests do not always pinpoint the problem; sensitive and specific measurements are needed to probe the individual components participating in gas-exchange for a better understanding of pathophysiology, disease progression and response to therapy.

In vivo Xenon-129 gas-exchange magnetic resonance imaging (129Xe gas-exchange MRI) has the potential to overcome these challenges. When participants inhale hyperpolarized 129Xe gas, it has different MR spectral properties as a gas, as it diffuses through the alveolar membrane and as it binds to red-blood-cells. 129Xe MR spectroscopy and imaging provides a way to tease out the different anatomic components of gas-exchange simultaneously and provides spatial information about where abnormalities may occur.

In this thesis, I developed and applied 129Xe MR spectroscopy and imaging to measure gas-exchange in the lungs alongside other clinical and imaging measurements. I measured 129Xe gas-exchange in asymptomatic congenital heart disease and in prospective, controlled studies of long-COVID. I also developed mathematical tools to model 129Xe MR signals during acquisition and reconstruction. The insights gained from my work underscore the potential for 129Xe gas-exchange MRI biomarkers towards a better understanding of cardiopulmonary disease. My work also provides a way to generate a deeper imaging and physiologic understanding of gas-exchange in vivo in healthy participants and patients with chronic lung and heart disease.

Summary for Lay Audience

Gas-exchange is the primary function of the lung, where breath moves down the airways, into sacs called alveoli, through the surrounding tissue membrane and into the tiniest blood vessels, called capillaries, where oxygen binds to red-blood-cells (RBC). Diseases can affect each of these steps but most techniques to detect gas-exchange only look at the whole process. Therefore, the development of new imaging tools may help to probe the individual steps in gas exchange to study disease and treat patients. Current tools for imaging the lung only look at ventilation or cannot measure all the way to the alveoli, the air sacs at the end of airways. A new way to probe the alveoli is by using a magnetized gas called xenon-129, which can act like oxygen and undergo gas-exchange. Since xenon also passes into the bloodstream and attaches to RBC, this technique also allows us to learn about each individual step of Gas-exchange. Magnetic resonance imaging (MRI) can be used to measure xenon in each compartment to determine the effectiveness of gas exchange, as well as providing maps of lung function to locate diseased regions of the lung. In this thesis, I used xenon MRI to measure gas-exchange and compare results with current imaging and breath-analysis tools. Specifically, I built mathematical tools to model how gas-exchange measurements are detected by xenon MRI. I then applied this technique in people with long-COVID and in a case of a congenital heart defect. Together, this work demonstrates the potential of xenon MRI for understanding gas-exchange in pulmonary and heart disease.

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