Introduction

Lung compliance is one of the most important parameters that reflect the elastic properties of the lung. Current clinic methods could only provide the global measurement of lung compliance, while the imaging modalities have the potential in regional assessment of the lung compliance. Hyperpolarized (HP) ¹²⁹Xe MRI has been widely used in pre-clinical research in recent years, it has inherent advantages in measuring the lung volume ^1,2. Previous study has demonstrated the ability of HP ¹²⁹Xe MRI in measuring global lung compliance³. Herein, we proposed a method for obtaining regional lung compliance using HP ¹²⁹Xe MRI, and the feasibility of the proposed method for evaluating the lung compliance changes caused by fibrosis was also demonstrated.

Methods

Twenty Sprague Dawley rats were divided into two groups. The fibrosis group were treated with 0.4 mL solution of bleomycin, and the control group were treated with an equivalent amount of normal saline. HP ¹²⁹Xe MRI was performed on all the rats from 21 to 23 days after treatment. For ¹²⁹Xe MRI, multi-slice 2D fast low angle shot sequence was used to acquire the ventilation images with different airway pressures using the following parameters: FOV = 5 cm×5 cm, matrix = 64 × 64, FA = 12°, TE/TR = 2.7/177.3 ms, slice thickness = 1.6 mm, interslice distance = 1.6 mm, and number of slices = 24. For each rat, the ventilation images at different airway pressures were registered to the images with minimal pressure using Advanced Normalization Toolkit⁴. Jacobian determinant maps were derived from diffeomorphic transformation which pulled the affine transformed different pressures ventilation images toward the reference images. Regional lung volume changes were depicted by multiplying the Jacobian determinant maps to the voxel size. The 3D distribution of lung compliance (C_map) was obtained by fitting the lung volume change maps with corresponding pressures to the equation of CXe = △V/△P pixel-by-pixel, where the V is the lung volume and the P is the breath-holding airway pressure recorded by a home-built ¹²⁹Xe delivery system. Apart from HP ¹²⁹Xe MRI, CT images were also acquired as cross-validation of fibrosis, and the acquisition parameters were as follows: tube voltage = 120 kV, FOV = 6 cm, spatial resolution = 0.5×0.5×0.5 mm³.

Results

Typical ventilation and CT images from fibrosis and control groups with different airway pressures were shown in Figure 1. As the airway pressure increased, obvious lung expansion could be observed. Figure 2 showed the representative C_map (5 of 24 slices were shown for each rat). Higher compliance was observed in the basal areas of control rat, while the distribution of lung compliance was relatively homogeneous in fibrosis rats. The mean compliance in fibrosis group was significantly lower than that in control group ((2.60 ± 0.78) × 10^-5 mL/cm H₂O vs. (4.31 ± 0.59) × 10^-5 mL/cm H₂O; p < .001).

Discussion and conclusion

In this study, we proposed a method for measuring regional pulmonary compliance using HP ¹²⁹Xe MRI. Significant difference was found in the pulmonary compliance derived by ¹²⁹Xe ventilation images between the fibrosis and control group. These results indicate the proposed method might enhance our understanding of pulmonary compliance changes caused by restrictive lung diseases, such as fibrosis.

Acknowledgements

This work is supported by National Natural Science Foundation of China (91859206, 21921004, 81825012), National key Research and Development Project of China (2018YFA0704000), Key Research Program of Frontier Sciences (ZDBS-LY-JSC004) and Scientific Instrument Developing Project of the Chinese Academy of Sciences (GJJSTD20200002, YJKYYQ20200067), CAS. Haidong Li acknowledges the support from Youth Innovation Promotion Association, CAS (2020330). Xin Zhou acknowledges the support from the Tencent Foundation through the XPLORER PRIZE.