3D Single-Breath Chemical Shift Imaging (3D SB-CSI) is capable of non-invasively assessing regional lung ventilation and gas uptake/exchange within a single breath-hold typically less than 13 seconds. This method uses a combination of MR spectroscopic imaging and hyperpolarized xenon-129 gas (HP Xe-129) to detect MR spectral peaks corresponding to Xe-129 dissolved in the lung parenchyma (tissue) and red blood cells (RBCs) [1-2]. From this study, we present preliminary clinical results of 3D SB-CSI from healthy, cystic fibrosis (CF), interstitial lung disease (ILD), and lung cancer (LC) subjects.A total of 42 subjects underwent HP Xe-129 3D SB-CSI: 17 healthy, 14 CF, 8 ILD, and 3 LC. Imaging was performed on 1.5T and 3T clinical systems (Avanto and Trio, Siemens Medical Solutions) with a transmit/receive RF coil (Clinical MR Solutions) tuned to the frequency of Xe-129. Enriched (~87%) Xe-129 was polarized to ~40% using a commercial prototype polarizer (XeMed LLC). The 3D SB-CSI sequence parameters were, TR/TE: 23.3ms/1.0ms, matrix: 128x128x6 voxels (after in-plane interpolation), FOV: 280-320mm2, and slice thickness: 20-25mm. Matlab (Mathworks, Natick, MA) was used for all post-processing.

Three peaks were typically found in the HP Xe-129 3D SB-CSI spectrums of healthy subjects: gas (0 ppm), tissue (197 ppm), and RBC (216 PPM). The tissue and RBC peaks had a larger 180^o phase separation at 3T compared to their 90^o phase separation at 1.5T(Fig. 1). The average difference in the mean tissue/RBC ratio between 1.5T and 3T acquisitions of the same subject was 7% for healthy and diseased subjects.

In the tissue/RBC maps of healthy subjects, there was a homogenous distribution of ratio values throughout the lungs, and no ventilation defects were found. However, in tissue/RBC maps for CF subjects, there was a heterogeneous distribution with regions of elevated ratio values, and ventilation defects were present (Fig. 2). These regions of high ratio values were indicative of regional gas transfer impairment caused by the disease. The mean whole lung tissue/RBC of healthy subjects (2.5 ± 0.16) was significantly lower than those of CF (3.1 ± 0.25). Moreover, there was a statistical difference between the mean tissue/RBC ratio for the healthy subjects and that for CF subjects for each slice position (p < 0.05).

Similar to the CF subjects, the tissue/RBC maps for ILD subjects had a heterogeneous distribution with regions of elevated ratio values (Fig. 3). The whole lung mean tissue/RBC of ILD subjects (4.9 ± 1.36) and mean tissue/RBC for each slice was statistically different from those of healthy subjects (p<0.05). Furthermore, there was a clear difference in the tissue/RBC and FVC %predicted between healthy and ILD subjects leading to the formation of two distinct clusters. However, the tissue/RBC ratio was more sensitive to pathophysiological changes in ILD subjects than the FVC %predicted (Fig 4).

In one LC subject, we identified a new peak at 97 ppm that was related with the presence of a lung tumor. The location of this tumor in the CSI map was well-matched with the tumor's location in the proton image (Fig. 5). Proton images were acquired in the same breath hold as the 3D SB-CSI acquisition.

Here, we demonstrate that hyperpolarized Xe-129 3D SB-CSI is feasible at 3T and produces similar results at 1.5T and 3T for the same subject (Fig. 1). Regions of impaired gas exchange were observed in the tissue/RBC maps of CF and ILD subjects (Figs. 2, 3). Healthy subjects had a significantly lower mean tissue/RBC compared to those of CF and ILD subjects (p < 0.05). A new peak at 97 ppm related to the presence of a lung tumor was identified, and could potentially serve as a biomarker for evaluating tumor pathophysiology (Fig. 5). Having novel information on regional changes in ventilation and gas uptake-exchange allows for a better understanding of lung physiology, disease progression, and treatment efficacy.