Regional mapping of gas uptake by blood and tissue in the human lung using hyperpolarized xenon-129 MRI

Abstract

Purpose: To develop a breathhold acquisition for regional mapping of ventilation and the fractions of hyperpolarized xenon-129 (Xe129) dissolved in tissue (lung parenchyma and plasma) and red blood cells (RBCs), and to perform an exploratory study to characterize data obtained in human subjects.

Materials and methods: A three-dimensional, multi-echo, radial-trajectory pulse sequence was developed to obtain ventilation (gaseous Xe129), tissue, and RBC images in healthy subjects, smokers, and asthmatics. Signal ratios (total dissolved Xe129 to gas, tissue-to-gas, RBC-to-gas, and RBC-to-tissue) were calculated from the images for quantitative comparison.

Results: Healthy subjects demonstrated generally uniform values within coronal slices, and a gradient in values along the anterior-to-posterior direction. In contrast, images and associated ratio maps in smokers and asthmatics were generally heterogeneous and exhibited values mostly lower than those in healthy subjects. Whole-lung values of total dissolved Xe129 to gas, tissue-to-gas, and RBC-to-gas ratios in healthy subjects were significantly larger than those in diseased subjects.

Conclusion: Regional maps of tissue and RBC fractions of dissolved Xe129 were obtained from a short breathhold acquisition, well tolerated by healthy volunteers and subjects with obstructive lung disease. Marked differences were observed in spatial distributions and overall amounts of Xe129 dissolved in tissue and RBCs among healthy subjects, smokers and asthmatics.

Keywords: gas uptake; hyperpolarized xenon-129; lung imaging; pulmonary disease.

Copyright © 2013 Wiley Periodicals, Inc.

Figures

Figure 1

Timing diagram showing one repetition of the multi-echo 3D radial pulse sequence for acquiring dissolved-phase and gas-phase Xe129 images. During each TR, three echoes (a half-echo and two symmetric echoes) of dissolved-phase data are collected for calculation of tissue and RBC images, followed by two echoes (a half-echo and a symmetric echo) of gas-phase data for calculation of ventilation images and a field map. The frequency offset of the RF pulses from resonance is indicated by Δf.

Figure 2

Theoretical prediction of the effect of a difference between the T2* for RBCs and that for tissue on the accuracy of tissue/RBC separation using the Hierarchical IDEAL algorithm. The predicted percentage error is shown as a function of the true (input value for the calculation) RBC fraction and the difference in T2* values, assuming a typical T2* value of 2.2 msec for tissue. For typical in-vivo values for T2* differences and RBC fractions (Table 2), the expected error is approximately 3% or less.

Figure 3

Representative coronal gas, tissue and RBC images from a healthy subject (H2). The RBC signal from the left ventricle of the heart (right image) was clearly seen in this subject.

Figure 4

(a) Coronal gas, tissue and RBC images covering the whole lung, and (b) corresponding tissue-to-gas, RBC-to-gas and RBC-to-tissue ratio maps from a healthy subject (H3). While dissolved-phase signal intensities and ratio values were generally uniform within each coronal slice, the tissue and RBC images, as well as tissue-to-gas and RBC-to-gas ratio maps, showed an anterior-to-posterior gradient associated with the gravity-dependent gradient in lung tissue density in the supine position.

Figure 5

Calculated slice-by-slice ratios for all healthy subjects. Plots are shown of the mean values for (a) total dissolved-phase to gas, (b) tissue-to-gas, (c) RBC-to-gas, and (d) RBC-to-tissue ratios for each coronal slice as a function of position along the anterior-posterior (A–P) direction. A value of 0 for A–P position corresponds to the most anterior slice and 1 corresponds to the most posterior slice. Subject H3 was imaged twice on the same day; H3* denotes repeat imaging for this subject. The values for this subject are plotted using dashed lines. The values of all ratios for subject H5, who was much older than subjects H1-H4 (Table 1), were generally lower than those for the other healthy subjects.

Figure 6

Whole-lung ratio values for all subjects. Means (denoted by plotting symbols) and standard deviations (vertical bars denote ± 1 standard deviation) are shown for (a) total dissolved-phase to gas, (b) tissue-to-gas, (c) RBC-to-gas, and (d) RBC-to-tissue ratios. Healthy subjects, asthmatics and smokers are shown in black, blue and red, respectively. Except for the RBC-to-tissue ratio, the mean ratios for asthmatics and smokers were generally lower than those in healthy subjects. These differences were statistically significant (see text). Only the total dissolved-phase to gas ratio is shown for subject S3 because the dissolved-phase signal intensities for this subject were too low to permit accurate separation of the tissue and RBC components (see text for additional explanation).

Figure 7

Calculated slice-by-slice ratios for smokers and asthmatics. Plots are shown of the mean values for (a) total dissolved-phase to gas, (b) tissue-to-gas, (c) RBC-to-gas, and (d) RBC-to-tissue ratios for each coronal slice as a function of position along the anterior-posterior (A–P) direction. A value of 0 for A–P position corresponds to the most anterior slice and 1 corresponds to the most posterior slice. Smokers are plotted in red and asthmatics are plotted in blue. For comparison, the solid black line shows the median of the respective ratio values for healthy subjects (Fig. 5). Subject S2 was imaged twice on the same day and subject A1 was imaged twice on different days; S2* and A1* denote repeat imaging for these subjects. The values for these subjects are plotted using dashed lines. Values for smoker S3 are not shown because the dissolved-phase signal intensities for this subject were too low to permit accurate separation of the tissue and RBC components (see text for additional explanation).

Figure 8

(a) Coronal gas, tissue and RBC images covering the whole lung, and (b) corresponding tissue-to-gas, RBC-to-gas and RBC-to-tissue ratio maps from subject S2 with COPD GOLD stage III. This subject showed numerous ventilation defects, as well as markedly inhomogeneous tissue and RBC images and ratio maps. The anterior-to-posterior gradient seen in healthy subjects was also absent.

Figure 9

(a) Coronal gas, tissue and RBC images, and (b) corresponding tissue-to-gas, RBC-to-gas and RBC-to-tissue ratio maps from asthmatic subjects A1 (age 53, left side of each panel) and A2 (age 16, right side of each panel). The homogeneity and overall values for the ratio maps for subject A1 were much different than those for subject A2, as seen by comparing the tissue-to-gas and RBC-to-tissue maps for the two subjects. Because the RBC-to-tissue ratios in subject A2 were higher than those in all other subjects, the corresponding ratio maps are presented on a scale of 0.0 to 1.0 (versus 0.0 to 0.7) so that features of the maps can be visualized.