Detection of Early Emphysema by Quantifying Lung Terminal Airways with Hyperpolarized 129Xe Diffusion MRI
Weiwei Ruan1, Jianping Zhong1, Ke Wang2, Yeqing Han1, and Xin Zhou1

1Wuhan Institute of Physical and Mathematics,Chinese Academy of Sciences, Wuhan, China, People's Republic of, 2Department of MRI, zhongnan hospital of wuhan university, Wuhan, China, People's Republic of

### Synopsis

To detect the early emphysema, hyperpolarized xenon diffusion MRI with multi-b values was used to quantify the lung terminal airways in five initial stages of emphysematous rats and five control rats. The DL (longitudinal diffusion coefficient), r, h, LM and S/V in the emphysematous group showed significant differences compared to those in the control group (P<0.05) and also exhibited a strong linear correlation (|r|>0.8) to Lm from histology for all the rats. The results showed multi-b diffusion MRI of hyperpolarized xenon has potential for the diagnosis of emphysema at the early stage.

### Purpose

To demonstrate the method of hyperpolarized (HP) xenon diffusion MRI with multi-b values to quantify the lung terminal airways in vivo in order to detect the emphysema at the early stage.

### Methods

Five rats induced by elastase for only 4 weeks and other five rats as the control group were used in the study. Eight b values (5，10，15，20，25，30，35，40 s/cm2) diffusion MRI (δ=Δ=2 ms) of HP xenon were completed in separate breath-holds. To reduce the influence caused by the difference between different b values beyond diffusion gradients, there were three images in one breath-hold for every b value. According to the theory proposed by Yablonskiy et al1,

$S=S_{0}\int_{0}^{\pi} \alpha\frac{\sin\alpha}{2}exp\left[-b\left(D_{L}\cos^{2}\alpha+D_{T}\sin^{2}\alpha\right)\right]d\alpha$

The anisotropic diffusion parameters were fitting pixel by pixel. Moreover, the parameter maps of lung terminal airways including R, r, h, S/V were obtained and the corresponding mean values were computed in the emphysematous group and control group. In order to improve the fitting accuracy of data, the effect of non-Gaussian signal behavior (dependence of DL and DT on b-value) has not been taken into account. Meanwhile, the lung was extracted and made into H&E-stained histological sections. The Lm from histology were computed for all the rats to evaluate the rationality and accuracy of the method in vivo to quantify the lung terminal airways with HP xenon diffusion MRI.

### Results

FIG.1 exhibits three representative interleaved 2D lung gradient-echo images acquired in one breath-hold. Due to the diffusion of xenon atoms in the lung, FIG.1b was much darker than that of FIG.1a and FIG.1c.

Table 1 lists the mean values of overall parameters including the Lm obtained from histology, the 129Xe anisotropic diffusion coefficients (DL, DT) and measured results of the lung terminal airways (R, r, h, LM, S/V) in the emphysematous group and the control group. The DL, r, h, LM and S/V showed a significant difference in the emphysematous group (p<0.05) compared to that in the control group. The result was consistent to that of Lm from histology (p<0.01), which indicated the significant pulmonary parenchymal destruction induced by elastase.

FIG.2 shows two representative images of H&E-stained lung histological sections from E_1 (A) and H_1 (B) mentioned in table 1. The results intuitively reflected the destruction, mainly the enlargement of pulmonary alveolus in the emphysema rat.

### Discussion

In this study, HP xenon diffusion MRI with eight b values was used to measure and quantitate the lung terminal airways of ten rats based on Weibel simplified lung model and the acquired parameters were used to detect the early stages of emphysema rats for the first time. The acquired parameters in control rats were consistent to that reported by previous studies with HP gas2,3,4. Meanwhile, the correlations between the acquired some parameters and the Lm from histology for all the rats were very well (|r|>0.8). It probably suggested that the reasonable extraction of morphometric parameters was allowed although the effect of non-Gaussian signal behavior (dependence of DL and DT on b-value) was ignored.

129Xe DL in the lungs of the emphysematous group showed significant differences compared to those of the control group but the DT did not. It was likely that the DL was more sensitive in the initial stages of emphysema than DT. It was speculated in the early emphysema, the change of lung structure was mainly expansion of terminal airways and collapse of alveolus but without substantial lung tissue destruction and the pulmonary acinar deformation.

Besides a lower SNR, 129Xe differs from 3He is that xenon can dissolve into the pulmonary capillary bloodstream, which would reduce the gas signal and affect the HP xenon diffusion MRI, especially with multi-b values. Therefore, it is very necessary to obtain an image with b=0 for every b value, which would reduce the influence caused by the difference of different b values beyond the different diffusion gradient strengths, such as xenon dissolution, T1 relaxation, radiofrequency depolarization and so on.

### Conclusion

The diffusion MRI of HP gas has shown very sensitive to the change of pulmonary parenchymal microstructure. The results in the study suggested that multi-b diffusion MRI with HP xenon in vivo is able to quantify the pulmonary micro-structure in alveolus and has potential for the diagnosis of emphysema at the early stage.

### Acknowledgements

No acknowledgement found.

### References

1. D. A. Yablonskiy, A. L. Sukstanskii, et al. Quantitative in vivo assessment of lung microstructure at the alveolar level with hyperpolarized 3He diffusion MRI. Proc Natl Acad Sci U S A, 2002. 99(5): 3111-6.

2. J. C. Woods, C. K. Choong, et al. Hyperpolarized 3He diffusion MRI and histology in pulmonary emphysema. Magn Reson Med, 2006. 56(6): 1293-300.

3. W. Wang, N. M. Nguyen, et al. Imaging lung microstructure in mice with hyperpolarized 3He diffusion MRI. Magn Reson Med, 2011. 65(3): 620-6.

4. A. Ouriadov, M. Fox, et al. Early stage radiation-induced lung injury detected using hyperpolarized Xe Morphometry: Proof-of-concept demonstration in a rat model. Magn Reson Med, 2015. doi:10.1002/mrm.25825.

### Figures

Fig.1. Representative three interleaved 2D gradient-echo images in one breath-hold. (a) the first image with b=0 s/cm2; (b) the second image with b = 40 s/cm2 and the diffusion gradient field strengths is 122 mT/m; (c) the third image with b=0 s/cm2 again.

Table 1. The overall list of Lm from histology and corresponding obtained parameters with diffusion HP Xenon MRI in the lungs of the emphysematous rats (n=5) and the healthy rats (n=5)

Fig.2 Representative images of H&E-stained lung histological sections under the microscope (Nikon Eclipse Ts 100). The magnification was 200. (A) a representative emphysema rat. (B) a representative healthy rat. Note the enlarged airspaces in the emphysematous rat.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
2022