Characterizing the Temporal Dynamics of 129Xe Spectroscopy to Uncover the Origins of Gas Exchange Impairment
129Xe MRI has emerged as a promising means of imaging ventilation distribution. Recently, interest has turned from only imaging ventilation to exploring solubility and chemical shifts to characterize gas exchange, including images of gas exchange patterns that are sensitive to a wide array of disease. The next challenge is to differentiate the underlying causes of gas exchange impairment to begin enabling not just detection, but diagnosis. This prompted us to investigate the relatively unexplored dynamics of 129Xe spectroscopy.
Hyperpolarized 129Xe is a powerful noninvasive tool for studying the physiological environment of the lung due to its distinct chemical shifts as xenon diffuses from the airspaces, through the alveolar membrane, and into red blood cells (RBCs). Previous work has shown that the spectral characteristics (amplitude, chemical shift, line width, and phase) of each resonance are sensitive to disease. In principle, the dynamic variations in four spectral parameters of each 129Xe resonance detected over inhalation, breath hold, and cardiac cycle can contain vital information on the origins of reduced lung function. In this work, our objective was to a) develop a framework for evaluating dynamics, b) assess temporal differences in spectroscopic parameters between patients with idiopathic pulmonary fibrosis (IPF) and healthy volunteers, c) understand the interplay between lineshape and dynamics, and d) create metrics to test the sensitivity of dynamic spectroscopy to underlying lineshapes and signal to noise.
The developed analysis methods were used to characterize the spectral dynamics of 14 healthy volunteers and 10 subjects with IPF. In all subjects, the breathing maneuver (inhale, breath hold, exhale) was reflected in the chemical shift and line width of the 129Xe RBC, barrier, and gas resonances. When comparing a representative IPF and healthy subject, we found that the subject with IPF had an RBC chemical shift that was initially 2 ppm lower and decreased by 0.5 ppm throughout a 5 s breath hold. Over the breath hold, we observed oscillations at the cardiac pulsation frequency in all of the spectral parameters of the RBC resonance. A mean peak-to-peak change of 7.9% ± 2.8% in amplitude of the RBC resonance was consistent across both cohorts. However, the oscillations in the chemical shift and phase of subjects with IPF were three times higher than in healthy volunteers. In light of the known relationship between RBC chemical shift and blood oxygenation levels, these findings suggest that we are sensitive to pathologically driven changes in blood oxygenation on the timescale of the cardiac cycle.
To analyze the effects of our spectral analysis in comparison to a known spectral model, we developed a digital dynamic spectroscopy phantom that simulated clinical free induction decays (FIDs) similar to what we collect during a dynamic spectroscopy acquisition based on specified spectral parameters. This phantom was used to validate our analysis techniques and explore the dependence of RBC signal oscillations on spectral structure. Additionally, motivated by a recent report that dissolved-phase xenon spectra is best fit to three dissolved-phase peaks, we performed a lineshape analysis on stationary spectra from a data set with higher spectral resolution. It was concluded that fitting to non-Lorentzian line shapes reduced the residual error of the fit and that the barrier resonance can potentially be represented by a linear combination of two Lorentzians where the spectral characteristics of the second peak are completely dependent on the first.
129Xe dynamic spectroscopy can be used to evaluate the temporal variations in gas exchange, although additional work must be done to properly characterize the spectral structure. The derived dynamic metrics have the potential to be useful biomarkers for disease progression and help discriminate between different pathologies that affect gas exchange.
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