Development of Hyperpolarized Xenon-129 Imaging Approaches for Assessing Lung Transplantation
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Graduate group
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Medical Sciences
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Hyperpolarized Xenon-129
Lung Imaging
Lung Transplantation
MRI
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Abstract
Despite noticeably improved early survival rates among lung transplant recipients, those of chronic lung allograft dysfunction (CLAD) and late mortality remain high. CLAD, in particular, is the leading cause of death after the first year post-lung transplantation and the primary limitation to long-term survival. Unfortunately, there is currently no proven therapy for successful CLAD management once diagnosed, though early diagnosis can potentially enable the refinement of treatment strategies to reverse or prevent risk factors before irreversible damage occurs. CLAD remains clinically difficult to diagnose, as spirometry, the current gold standard diagnostic, has low sensitivity for detecting early pathologic changes in small airways and is dependent on patient effort. There is therefore a need for a diagnostic tool capable of detecting CLAD-related lung deterioration in a safe and timely manner in order to improve patient management. Hyperpolarized xenon-129 (HXe) MRI has already been proven sensitive to a variety of lung pathologies that affect lung ventilation and xenon gas exchange, taking advantage of the chemical shifts xenon exhibits moving from the airways (gas-phase) into the parenchyma (dissolved-phase). Directly imaging dissolved-phase (DP) HXe remains challenging, however, due to poor signal and spatial resolution as a consequence of the relatively low concentration of xenon that dissolves into the lung parenchyma. Alternatively, gas exchange can be imaged indirectly at higher signal with Xenon-polarization Transfer Contrast (XTC) MRI by observing the loss of gas-phase (GP) signal after saturating the DP resonance. Traditionally, XTC imaging has involved saturating both DP resonances simultaneously within one or two long breath-holds. In this work, we further developed the XTC technique for selectively saturating either the tissue membrane or red blood cell (RBC) resonance, enabling more specific quantification of gas exchange, and subsequently expanded XTC imaging to incorporate a multi-breath protocol more closely resembling natural breathing—decreasing the burden on the subjects by eliminating long breath-holds. These developments provide more comprehensive lung function measurements than previously achievable with this technique and were assessed longitudinally in lung transplant recipients. Comparisons with spirometry allowed us to identify potential HXe imaging markers reflecting the pathological changes associated with transplant recovery and decline, which may indicate early inflammatory or fibrotic changes characteristic of CLAD.