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. 2021 Sep 15;7(3):452-465.
doi: 10.3390/tomography7030039.

Evaluation of Regional Lung Function in Pulmonary Fibrosis with Xenon-129 MRI

Jaime Mata  1 , Steven Guan  1 , Kun Qing  1 , Nicholas Tustison  1 , Yun Shim  1   2 , John P Mugler 3rd  1 , Talissa Altes  3 , Jhosep Huaromo  1 , Borna Mehrad  4
Affiliations

Evaluation of Regional Lung Function in Pulmonary Fibrosis with Xenon-129 MRI

Jaime Mata et al. Tomography. .

Abstract

Idiopathic pulmonary fibrosis, a pattern of interstitial lung disease, is often clinically unpredictable in its progression. This paper presents hyperpolarized Xenon-129 chemical shift imaging as a noninvasive, nonradioactive method of probing lung physiology as well as anatomy to monitor subtle changes in subjects with IPF. Twenty subjects, nine healthy and eleven IPF, underwent HP Xe-129 ventilation MRI and 3D-SBCSI. Spirometry was performed on all subjects before imaging, and DLCO and hematocrit were measured in IPF subjects after imaging. Images were post-processed in MATLAB and segmented using ANTs. IPF subjects exhibited, on average, higher Tissue/Gas ratios and lower RBC/Gas ratios compared with healthy subjects, and quantitative maps were more heterogeneous in IPF subjects. The higher ratios are likely due to fibrosis and thickening of the pulmonary interstitium. T2* relaxation was longer in IPF subjects and corresponded with hematocrit scores, although the mechanism is not well understood. A lower chemical shift in the red blood cell spectroscopic peak correlated well with a higher Tissue/RBC ratio and may be explained by reduced blood oxygenation. Tissue/RBC also correlated well, spatially, with areas of fibrosis in HRCT images. These results may help us understand the underlying mechanism behind gas exchange impairment and disease progression.

Keywords: MRI; hyperpolarized Xenon-129; idiopathic pulmonary fibrosis; interstitial lung disease.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
A comparison of the segmented ventilation images for a single healthy (H2) (A) and IPF (I2) subject (B). The healthy subject has mainly areas of normal (green) ventilation, with hypoventilation (orange) and no ventilation (red) areas located on the periphery of the lung, occupying 4.8% of the total lung volume for this particular subject. In the IPF subject, these large ventilation defects located on the periphery of the lung encroach toward the center of the lung, occupying 35.1% of the total lung volume. The IPF subject retained a portion of the inhaled xenon in the trachea and bronchi, resulting in the high intensity of gas in those areas (not shown). The segmentation algorithm excluded these regions to avoid overestimating the volume of the lungs and areas of ventilation.
Figure 2
Figure 2
Coronal maps of ventilation and 3D-SBCSI Tissue/RBC, Tissue/Gas, and RBC/Gas in (A) healthy subject H4 and (B) IPF subject I8.
Figure 3
Figure 3
Distribution of average (A) Tissue/Gas, (B) Tissue/RBC, and (C) RBC/Gas ratios for healthy and IPF subjects. IPF subjects typically had a significantly increased average Tissue/Gas and Tissue/RBC ratio (p < 0.01) and a decreased average RBC/Gas ratio (p < 0.05). The distribution of average Tissue/RBC ratios was larger in IPF than healthy subjects. The uppermost outlier in (A) represents subject H8. * represents p < 0.05 and ** represents p < 0.01.
Figure 4
Figure 4
Coronal maps of 3D-SBCSI Tissue T2*, RBC T2* in (A) healthy subject H4 and (B) IPF subject I1.
Figure 5
Figure 5
Coronal maps of 3D-SBCSI Tissue Chemical Shift (CS), RBC Chemical Shift in a (A) healthy subject H4 and (B) IPF subject I9. The respective chemical shift maps were normalized to show how each voxel deviated from their expected tissue chemical shift (197 ppm) and RBC chemical shift (216 ppm).
Figure 6
Figure 6
Distribution of average (A) Tissue T2*, (B) RBC T2*, (C) Tissue CS, (D) RBC-Tissue CS and (E) RBC CS for healthy and IPF subjects. ** represents p < 0.01.
Figure 7
Figure 7
(A) FVC predicted and the Tissue/RBC ratio were significantly and strongly correlated between healthy (green), healthy but low PFT (yellow), and IPF (red) subjects (R = −0.78). (B) There was also a significant strong correlation between FEV1 predicted and the Tissue/RBC ratio (R = −0.76). (C) DLCO and the Tissue/RBC ratio (R = −0.85) were also significantly strongly correlated. (D) FVC predicted and the RBC chemical shift were significantly correlated (R = 0.84). (E) There was another significant and strong correlation between FEV1 predicted and the RBC chemical shift (R = 0.79). (F) DLCO and the RBC Chemical Shift (R = 0.86) were also significantly correlated. The solid line represents a linear regression of the data, while the dashed lines shows the 95% confidence interval of the linear regression.
Figure 8
Figure 8
Central coronal slice of the Tissue/RBC maps (A) and spatially matched coronal HRCT images (B) from IPF subject I6. Due to the difference in the slice thickness between the Tissue/RBC maps (15 mm) and HRCT images (0.7 mm), information from multiple nearby HRCT images could appear in a single slice of the Tissue/RBC maps. Each arrow points to a region of high Tissue/RBC, and the same color arrow points to the corresponding region of fibrosis in the HRCT images.
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