Purpose

Apparent alveolar septal wall thickness (SWT) measurements obtained with hyperpolarized xenon-129 (HXe) MRI are sensitive to inflammatory or fibrotic pathologies in the lung parenchyma^1-7. Such measurements are typically conducted in the form of global spectroscopy acquisitions that lack spatial information. In recent years, efforts have been made to obtain regional maps of SWT^8,9. However, the analytical models used to extract this metric from the acquired xenon gas uptake measures are all based on the assumption of unidirectional gas transfer from the alveoli to the lung parenchyma, with subsequent xenon accumulation in the downstream blood pool. While such assumptions are a reasonably accurate description for the lung as a whole when assessed with global spectroscopy, these prerequisites break down at the regional level, where the xenon signal in more central lung volumes might also be affected by inflowing blood from the periphery. In this work, we investigated whether there is a regional difference in the observed apparent gas uptake between peripheral and central lung regions.

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 a 1D-projection gradient-echo sequence with left-to-right frequency encoding that employed a non-selective 700-μs Gaussian RF excitation pulse centered at the dissolved phase (DP) resonance 3,530 Hz downfield from the gas-phase resonance. Taking advantage of the large frequency difference between the two phases combined with a sufficiently small acquisition bandwidth, HXe in the pulmonary air spaces and dissolved in the lung tissue were imaged simultaneously, side-by-side^10-12. The following sequence parameters were used: matrix size 1920×80; TE 2.6 ms; FOV 220 mm; receiver bandwidth 120 Hz/pixel; flip angle 7°, TR 10 ms (TR_90°,equiv 1.3 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. Septal wall thickness and capillary transit time were calculated using the analytical uptake model of Patz et al.¹³, based on the recovery of the averaged dissolved-phase signal following each saturation pulse. 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 1a shows the normalized 1D DP signal in the rabbit lung as a function of time following saturation of the DP magnetization. The signal within the cardiac cavity was set to zero due to its low signal-to-noise ratio. For clarification, the DP signals of just the edges of the lung are plotted in Fig. 1b. While the xenon accumulation in the periphery of the lung levels off following the initial filling phase, the xenon signal at the center of the lung keeps increasing, indicating a continued inflow of DP magnetization from the blood flow towards the heart. These discrepancies in gas accumulation dynamics are reflected in an apparent drop of the extracted capillary transit time (Fig. 1c) and an apparent increase in alveolar SWT (Fig. 1d), respectively, from the periphery towards the center. Since in a healthy lung no such outside-in asymmetry of transit time and SWT is plausible, it most likely can be attributed to regional differences in gas transport dynamics.

Conclusion

We demonstrated an implausible change in observed capillary transit time and SWT from the periphery to the center of the lungs. This effect is likely caused by the transport of xenon-saturated blood towards the heart, giving rise to an unaccounted signal increase that biases the model-based parameter extraction and is not based on physiological differences. Our measurements indicate that the assumptions underlying the existing analytical gas-transport models are violated in the case of spatially resolved SWT measurements. We therefore conclude that the extraction of consistent SWT maps from regional xenon gas uptake images necessitates a fundamental revision of these models.

Acknowledgements

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

References

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