Introduction

As an important monitoring indicator in lung diseases such as ARDS and IPF, pulmonary compliance is widely used to guide the setting of positive end-expiratory pressure of ventilator. Pulmonary compliance is defined as the lung volume change per unit pressure change and is generally measured by pulmonary function tests (PFTs). Hyperpolarized (HP) ¹²⁹Xe ventilation imaging is a new technique used in pre-clinical research, and it can be utilized to obtain lung ventilated volume and ventilation defect percentage accurately^1,2. In this study, a strategy for quantifying pulmonary compliance using HP ¹²⁹Xe ventilation imaging was proposed and the feasibility of the strategy for distinguishing lung fibrosis in rats was also demonstrated.

Methods

Ten Sprague Dawley rats were divided into two groups. The experimental group was intratracheally instilled with bleomycin solution (2.5U/kg body weight) to induce lung fibrosis while the control group was treated with an equivalent amount of normal saline (NS, 0.4 ml). PFTs and HP ¹²⁹Xe MRI were performed on all rats on 21 ~ 24 days after instillation. For PFTs measurements, quasi-static pulmonary compliance (Cchord) was measured three times for each rat using a forced maneuvers system (CRFM 100, EMMS, UK). For HP ¹²⁹Xe MRI experiments, pulmonary compliance was determined as the Cst-Xe = △V/△P_plat, where the V is the lung volume calculated from ventilation images and the P_plat is the breath-holding airway pressure recorded by a home-built ¹²⁹Xe delivery system. To avoid the effect of T₁ relaxation of ¹²⁹Xe signal on volume calculation, each set of ventilation images was acquired in different breath-holding pressure after an appropriate number of xenon gas pre-breaths. The parameters of ventilation imaging were as follows: FOV = 5 cm, matrix=64×64, α=12°, TE=2.2 ms, slice thickness = 1.6 mm, number of slices = 24. The ventilation images were segmented using the Otsu algorithm to calculate the lung volume at different P_plat. Then the Cst-Xe was calculated using the slope of the Pressure-Volume curve. In addition, HP ¹²⁹Xe diffusion-weighted imaging (DWI) was also performed on all rats to verify the bleomycin-induced fibrosis. The parameters of DWI were as follow: FOV = 6 cm, matrix=64×64, α=10°, TE=3.5 ms, ramp up/down time = 0.123 ms, constant time = 0.7 ms, diffusion time = 1.2 ms, five b values used were 0, 8, 16, 24 and 32 s/cm². The DWI images were fitted to the cylinder model³ to obtain the microstructural parameters of the lung.

Results

The measured Cchord using PFTs showed significant difference between bleomycin and NS rats (0.67 ± 0.12 ml/cm H₂O vs. 1.27 ± 0.15 ml/cm H₂O, p < 0.001). Similarly, the Cst-Xe driven from HP ¹²⁹Xe ventilation imaging showed significant difference between the bleomycin and NS rats (0.25 ± 0.06 vs. 0.40 ± 0.05 ml/cm H₂O, p = 0.003). The representative ventilation images were shown in figure 1 (A), and the bleomycin rat lung inflated with the increased of P_plat is clearly slower than that of NS rat. Figure 1 (B) showed that the Cst-Xe correlated well with Cchord (r = 0.89, p = 0.001). Moreover, as the verification of the lung fibrosis, the obtained microstructural parameters from DWI images including inner radius (r), outer radius (R), mean airspace chord length (Lm) and surface-to-volume ratio (SVR) also showed significant difference (p ≤ 0.001) between the groups, and also correlated well with Cst-Xe (|r| > 0.08, p<0.01), as shown in figure 2.

Discussion and Conclusion

In this study, we proposed a strategy for measuring the pulmonary compliance using HP ¹²⁹Xe MRI. Pulmonary compliance driven by ¹²⁹Xe ventilation imaging showed significant difference between the bleomycin and NS rats, and correlated well with that measured using PFTs. In addition, strong correlation between Cst-Xe and the microstructural parameters from DWI was consistent with the histological results reported previously^4,5. These results demonstrated the feasibility of the proposed strategy in quantifying pulmonary compliance, which would improve our understanding of pulmonary compliance changes in lung diseases such as fibrosis.

Acknowledgements

This work was supported by National Key R&D Program of China (2018YFA0704000), National Natural Science Foundation of China (81625011, 91859206, 21921004, 81601491), Key Research Program of Frontier Sciences, CAS (QYZDY-SSW-SLH018) and Hubei Provincial Natural Science Foundation of China (2017CFA013, 2018ACA143).