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.

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 D_L and D_T 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.

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 (D_L, D_T) and measured results of the lung terminal airways (R, r, h, L_M, S/V) in the emphysematous group and the control group. The D_L, r, h, L_M 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.

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 gas^2,3,4. 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 D_L and D_T on b-value) was ignored.

¹²⁹Xe D_L in the lungs of the emphysematous group showed significant differences compared to those of the control group but the D_T did not. It was likely that the D_L was more sensitive in the initial stages of emphysema than D_T. 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.

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.