Assessment of lung function in asthma and COPD using hyperpolarized 129Xe chemical shift saturation recovery spectroscopy and dissolved-phase MRI

Abstract

Magnetic-resonance spectroscopy and imaging using hyperpolarized xenon-129 show great potential for evaluation of the most important function of the human lung -- gas exchange. In particular, chemical shift saturation recovery (CSSR) xenon-129 spectroscopy provides important physiological information for the lung as a whole by characterizing the dynamic process of gas exchange, while dissolved-phase (DP) xenon-129 imaging captures the time-averaged regional distribution of gas uptake by lung tissue and blood. Herein, we present recent advances in assessing lung function using CSSR spectroscopy and DP imaging in a total of 45 subjects (23 healthy, 13 chronic obstructive pulmonary disease (COPD) and 9 asthma). From CSSR acquisitions, the COPD subjects showed red blood cell to tissue-plasma (RBC-to-TP) ratios below the average for the healthy subjects (p < 0.001), but significantly higher septal wall thicknesses as compared with the healthy subjects (p < 0.005); the RBC-to-TP ratios for the asthmatic subjects fell outside two standard deviations (either higher or lower) from the mean of the healthy subjects, although there was no statistically significant difference for the average ratio of the study group as a whole. Similarly, from the 3D DP imaging acquisitions, we found that all the ratios (TP to gas phase (GP), RBC to GP, RBC to TP) measured in the COPD subjects were lower than those from the healthy subjects (p < 0.05 for all ratios), while these ratios in the asthmatic subjects differed considerably between subjects. Despite having been performed at different lung inflation levels, the RBC-to-TP ratios measured by CSSR and 3D DP imaging were fairly consistent with each other, with a mean difference of 0.037 (ratios from 3D DP imaging larger). In ten subjects the RBC-to-GP ratios obtained from the 3D DP imaging acquisitions were also highly correlated with their diffusing capacity of the lung for carbon monoxide per unit alveolar volume ratios measured by pulmonary function testing (R = 0.91).

Keywords: 3D dissolved-phase imaging; COPD; CSSR; asthma; gas uptake; hyperpolarized xenon-129; pulmonary imaging.

Copyright © 2014 John Wiley & Sons, Ltd.

Figures

Figure 1

(a) Pulse-sequence diagram for the CSSR spectroscopy acquisition. The DP magnetization is saturated by three narrow-bandwidth RF pulses centered at 198 ppm, 218 ppm and 208 ppm, which leave the GP magnetization largely undisturbed. Following a variable delay time τ an excitation RF pulse centered at 208 ppm is applied and an FID is collected (DAQ). (b) Representative xenon saturation-recovery gas-uptake curve (TP-to-GP ratio) as a function of delay time τ. The measurement data (squares) were fitted using a theoretical gas-uptake model described by Patz et al. in (20) (solid line).

Figure 2

(a) TP-to-GP ratio, (b) RBC-to-GP ratio, (c) RBC-to-TP ratio and (d) average septal wall thickness at 3 lung inflation levels as assessed by CSSR spectroscopy, averaged over 5 healthy subjects. All DP ratios were heavily dependent on lung inflation. At each inflation level, each of the TP-to-GP and RBC-to-GP ratios was significantly different from the others (p < 0.01) while the RBC-to-TP ratio was only significantly different between RV and TLC (p < 0.01). Changes in the septal wall thickness were not statistically significant.

Figure 3

Healthy subjects (including H12, in blue, who had a high exposure to second-hand smoke) and COPD subjects at various GOLD stages (GS) sorted by average septal wall thickness as measured by CSSR spectroscopy.

Figure 4

Average RBC-to-TP ratios obtained from CSSR spectroscopy for healthy (filled circles), asthmatic (open circles) and COPD (triangles) subjects at TLC. The solid line marks the mean value for the healthy subjects while the dashed lines indicate 1 or 2 standard deviations (SD) from the mean. Almost all subjects with lung disease fall outside the 2 standard deviation variation established by the healthy subjects.

Figure 5

3D DP Imaging: (a) total DP-to-GP, (b) TP-to-GP, (c) RBC-to-GP, and (d) RBC-to-TP ratios, averaged over the whole lung, for all subjects. Healthy subjects and asthma subjects are shown in black and blue, respectively, including the younger and older sub-groups. COPD subjects are shown in red, including GOLD stage 1 (GS 1) represented by round markers, and stages 2 and 3 (GS 2/3) represented by rectangular markers. COPD subject C6 had difficulty inhaling the total volume of gas, which resulted in a relatively low SNR in the third echo of DP images. As a consequence, the TP and RBC components could not be separated for this subject and only the DP-to-GP ratios are included. The 95% confidence intervals based on the results from all healthy subjects are indicated by solid black lines (STD = standard deviation).

Figure 6

(a) Images of HXe lung ventilation and HXe dissolved in TP and RBC compartments. (b) Corresponding TP-to-GP, RBC-to-GP and RBC-to-TP ratio maps acquired in healthy subject H6, COPD subjects C3 and C4, and asthma subjects A2 and A4. COPD subjects C3 and C4 showed numerous ventilation defects and had all ratios lower than those for the healthy subjects. Younger asthma subject A2 showed high RBC-to-TP ratios, as compared with healthy subjects. Similar to COPD subjects C3 and C4, the older asthma subject A4 had all ratios lower than those for the healthy subjects. In the apex of the right lung, this subject had high TP-to-GP ratios and low RBC-to-GP and RBC-to-TP ratios. Images adapted from (29) with permission.

Figure 7

RBC-to-GP ratios measured by 3D DP imaging versus the DLCO/Va ratios measured by pulmonary function tests.

Figure 8

Simulation results: (a, b) Dissolved-phase Xe129 gas-uptake curves for a septal wall thickness of 6 μm (a) or 20 μm (b). (c, d) Evolution of the dissolved-phase longitudinal-magnetization for the 3D acquisition at a septal wall thickness of 6 μm (c) or 20 μm (d). (e) Equivalent delay time corresponding to the steady state for the 3D acquisition versus septal wall thickness.

Figure 9

Bland-Altman plot of the mean RBC-to-TP ratios measured by 3D DP imaging at a lung inflation level of one-third FVC and by CSSR spectroscopy at TLC. The mean of the ratio difference (3D DP Imaging – CSSR spectroscopy) was 0.037 ± 0.036.