The spectral parameters of hyperpolarized 129Xe exchanging between airspaces, interstitial barrier, and red blood cells (RBCs) are sensitive to pulmonary pathophysiology. This study sought to evaluate whether the dynamics of 129Xe spectroscopy provide additional insight, with particular focus on quantifying cardiogenic oscillations in the RBC resonance. 129Xe spectra were dynamically acquired in eight healthy volunteers and nine subjects with idiopathic pulmonary fibrosis (IPF). 129Xe FIDs were collected every 20 ms (TE = 0.932 ms, 512 points, dwell time = 32 μs, flip angle ≈ 20°) during a 16 s breathing maneuver. The FIDs were pre-processed using the spectral improvement by the Fourier thresholding technique and fit in the time domain to determine the airspace, interstitial barrier, and RBC spectral parameters. The RBC and gas resonances were fit to a Lorentzian lineshape, while the barrier was fit to a Voigt lineshape to account for its greater structural heterogeneity. For each complex resonance the amplitude, chemical shift, linewidth(s), and phase were calculated. The time-averaged spectra confirmed that the RBC to barrier amplitude ratio and RBC chemical shift are both reduced in IPF subjects. Their temporal dynamics showed that all three 129Xe resonances are affected by the breathing maneuver. Most notably, several RBC spectral parameters exhibited prominent oscillations at the cardiac frequency, and their peak-to-peak variation differed between IPF and healthy volunteers. In the IPF versus healthy cohort, oscillations were more prominent in the RBC amplitude (16.8 ± 5.2 versus 9.7 ± 2.9%; P = 0.008), chemical shift (0.43 ± 0.33 versus 0.083 ± 0.05 ppm; P < 0.001), and phase (7.7 ± 5.6 versus 1.4 ± 0.8°; P < 0.001). Dynamic 129Xe spectroscopy is a simple and sensitive additional tool that probes the temporal variability of gas exchange and may prove useful in discerning the underlying causes of its impairment.

Background Assessing functional impairment, therapeutic response, and disease progression in patients with idiopathic pulmonary fibrosis (IPF) continues to be challenging. Hyperpolarized 129Xe MRI can address this gap through its unique capability to image gas transfer three-dimensionally from airspaces to interstitial barrier tissues to RBCs. This must be validated by testing the degree to which it correlates with pulmonary function tests (PFTs) and CT scores and its spatial distribution reflects known physiology and patterns of disease. Methods 13 healthy individuals (33.6±15.7 years) and 12 IPF patients (66.0±6.4 years) underwent 129Xe MRI to generate 3D quantitative maps depicting the 129Xe ventilation distribution, its uptake in interstitial barrier tissues, and its transfer to RBCs. For each map, mean values were correlated with PFTs and CT fibrosis scores and their patterns were tested for the ability to depict functional gravitational gradients in healthy lung, and to detect the known basal and peripheral predominance of disease in IPF. Results 129Xe MRI depicted functional impairment in IPF patients, whose mean barrier uptake increased by 188% compared to the healthy reference population. 129Xe MRI metrics correlated poorly and insignificantly with CT fibrosis scores, but strongly with pulmonary function tests. Barrier uptake and RBC transfer both correlated significantly with DLCO (r=−0.75, p<0.01 and r=0.72, p<0.01), while their ratio (RBC/barrier) correlated strongly (r=0.94, p<0.01). RBC transfer exhibited significant anterior-posterior gravitational gradients in healthy volunteers, but not in IPF, where it was significantly impaired in the basal (p=0.02) and sub-pleural (p<0.01) lung. Conclusions Hyperpolarized 129Xe MRI is a rapid and well-tolerated exam that provides region-specific quantification of interstitial barrier thickness and RBC transfer efficiency. With further development, it could become a robust tool for measuring disease progression and therapeutic response in IPF patients, sensitively and non-invasively.

Purpose: Hyperpolarized 129 Xe magnetic resonance imaging (MRI) using Dixon-based decomposition enables single-breath imaging of 129 Xe in the airspaces, interstitial barrier tissues, and red blood cells (RBCs). However, methods to quantitatively visualize information from these images of pulmonary gas transfer are lacking. Here, we introduce a novel method to transform these data into quantitative maps of pulmonary ventilation, and 129 Xe gas transfer to barrier and RBC compartments. Methods: A total of 13 healthy subjects and 12 idiopathic pulmonary fibrosis (IPF) subjects underwent thoracic 1 H MRI and hyperpolarized 129 Xe MRI with one-point Dixon decomposition to obtain images of 129 Xe in airspaces, barrier and red blood cells (RBCs). 129 Xe images were processed into quantitative binning maps of all three compartments using thresholds based on the mean and standard deviations of distributions derived from the healthy reference cohort. Binning maps were analyzed to derive quantitative measures of ventilation, barrier uptake, and RBC transfer. This method was also used to illustrate different ventilation and gas transfer patterns in a patient with emphysema and one with pulmonary arterial hypertension (PAH). Results: In the healthy reference cohort, the mean normalized signals were 0.51 AE 0.19 for ventilation, 4.9 AE 1.5 x 10 -3 for barrier uptake and 2.6 AE 1.0 9 10 -3 for RBC (transfer). In IPF patients, ventilation was similarly homogenous to healthy subjects, although shifted toward slightly lower values (0.43 AE 0.19). However, mean barrier uptake in IPF patients was nearly 29 higher than in healthy subjects, with 47% of voxels classified as high, compared to 3% in healthy controls. Moreover, in IPF, RBC transfer was reduced, mainly in the basal lung with 41% of voxels classified as low. In healthy volunteers, only 15% of RBC transfer was classified as low and these voxels were typically in the anterior, gravitationally nondependent lung. Conclusions: This study demonstrates a straightforward means to generate semiquantitative binning maps depicting 129 Xe ventilation and gas transfer to barrier and RBC compartments. These initial results suggest that the method could be valuable for characterizing both normal physiology and pathophysiology associated with a wide range of pulmonary disorders.

We describe a low-pressure flow-through apparatus for generating hyperpolarized 129 Xe and report its performance by examining both the output 129 Xe polarization P Xe by NMR and the in situ Rb polarization profile by optically detected electron paramagnetic resonance. The polarizer is based on a previously presented design employing a long optical pumping cell, lean Xe mixture at low pressure, Rb presaturation, and counterflow of gas with respect to the direction of light propagation. The numerical model to which we compare the polarizer's performance includes the temperature dependence of the Rb-129 Xe spin-exchange rate, which has not previously been treated. The qualitative trends in the data mostly follow those in the model, although the model predicts P Xe to be up to a factor of two higher than observed. This discrepancy cannot be attributed to low Rb polarization: the model and the optically detected electron paramagnetic resonance data ͑acquired at six points along the length of the heated portion of the optical pumping cell͒ are in reasonable agreement and show typical values of 85%-95%, although measurements also reveal an anomalous region of depressed Rb polarization near the middle of the cell. The highest output 129 Xe polarization P Xe =84Ϯ 16%, was recorded using Ϸ60 W of frequency-narrowed laser light at a Xe partial pressure ͑referenced to 20°C͒ of 1.1Ϯ 0.2 mbar, flowing at 1 sccm of Xe; typical values were P Xe Ϸ 20% flowing at 10 sccm of Xe with Ϸ30 W of laser light.