Purpose

Measurements of apparent alveolar septal wall thickness (SWT) obtained with hyperpolarized xenon-129 (HXe) MRI are sensitive to inflammatory or fibrotic pathologies in the lung parenchyma^1-8 but are also affected by lung inflation level⁹ as well as physiological variations throughout the breath hold. Here, we investigated the dependence of such measurements on the choice of acquisition parameters in a rabbit model.

Methods

Imaging experiments were performed in sedated New Zealand rabbits (approx. 4 kg). Animals were ventilated with room air until imaging began, at which point the gas mix was switched to 20% oxygen and 80% HXe for 5 breaths (6 ml/kg tidal volume), followed by an 8-s breath-hold at either end inspiration (EI) or end expiration (EE). All studies were approved by the Institutional Animal Care and Use Committee.
MR imaging was conducted using either a 1D-projection gradient-echo sequence with left-to-right frequency encoding or a chemical shift saturation recovery (CSSR) spectroscopy sequence. The former employed a non-selective 700-μs Gaussian RF excitation pulse centered 3,530 Hz downfield from the gas-phase resonance. The following sequence parameters were used: matrix size 640 or 1920×80; TE 2.6 ms; FOV 220 mm; receiver bandwidth 120 Hz/pixel; flip angle 7-16°, TR 10-50 ms (TR_90°,equiv 1.3 - 4 s¹⁰). During the breath hold, the dissolved-phase magnetization was saturated 6 times every 500 ms with 3 consecutive 3-ms frequency-selective Gaussian RF pulses centered at 200 ppm and separated by 1.2 ms spoiler gradients. CSSR measurements were conducted with either 8 or 40 delay times varying between 3 and 500 ms, following the same dissolved-phase saturation scheme. All other parameters were as described by Qing et al³. Septal wall thickness was calculated using the analytical uptake model of Patz et al.¹¹, based on the recovery of the averaged total dissolved-phase signal following each saturation pulse. For a direct qualitative comparison between EI and EE, the fitted analytical curves were normalized by the dissolved phase (DP) to gas phase (GP) ratio at a delay time of 100 ms. All MR studies were performed at 1.5T (Avanto; Siemens) using a custom xenon-129 transmit/receive birdcage coil (Stark Contrast, Erlangen, Germany). Enriched xenon gas (87% xenon-129) was polarized using a prototype commercial system (XeBox-E10, Xemed LLC, Durham, NH).

Results and Discussion

Figure 1 illustrates the qualitative differences in the fitted and normalized DP-GP ratios at EE vs EI for six acquisition schemes. In a conventional CSSR acquisition with 40 sequentially increasing delay times (Fig. 1a), a marked qualitative difference between EI and EE measurements is noticeable, which translates into a significant difference in the extracted SWTs (8.8 μm at EE, 12.7 μm at EI). However, if the CSSR study is repeated using only 8 delay times (Fig. 1b), the EE and EI curves are beginning to converge. Similar trends can be observed in the 1D measurements. In three acquisitions with similar TR_90°,equivs of approximately 1.3 s (Fig. 1c-e), the DP-GP ratio curves at EE and EI are converging as the excitation flip angle decreases. Finally, if the TR_90°,equiv is increased to 4 s (Fig. 1f), the EE and EI uptake curves and the associated gas exchange parameters become essentially indistinguishable. The key difference between the six performed measurements is the total number of DP saturations (in the CSSR studies) or the excitation flip angle (in the 1D studies). High flip angle RF pulses applied to the DP magnetization result in a regional depolarization of the GP magnetization due to gas exchange. This depolarization is therefore weighted by the spatially variable gas exchange efficiency in the lung, which is particularly large at EE. Thus, by preferentially destroying the GP magnetization in fast exchanging lung volumes, the MR acquisition itself imprints a time-varying bias onto the measured DP-GP ratio that is lung inflation-dependent. If this bias is minimized by using fewer RF saturations and/or decreasing the employed flip angles, however, the observed gas uptake curves become qualitatively identical and the dependence of the SWT on lung inflation vanishes. Sampling the entire uptake curve after each DP saturation, as performed for the 1D acquisition, proved to be particular robust.

Conclusion

We demonstrated the dependence of the observed pulmonary xenon gas uptake on the MR acquisition parameters. Measurements that employ high flip angles selectively destroy the GP magnetization in lung volumes with high gas exchange. If this effect is minimized, the previously reported SWT dependence on lung inflation disappears.

Acknowledgements

Supported by NIH grants R01 EB015767, R01 HL129805, S10 OD018203 and R01 CA193050.

References

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