Differentiating Early Stage and Later Stage Idiopathic Pulmonary Fibrosis using Hyperpolarized 129Xe Ventilation MRI
Mu He1, Scott H. Robertson2, Jennifer M. Wang3, Craig Rackley4, H. Page McAdams5, and Bastiaan Driehuys5

1Electrical and Computer Engineering Department, Duke University, Durham, NC, United States, 2Medical Physics Graduate Program, Duke University, Durham, NC, United States, 3School of Medicine, Duke University, Durham, NC, United States, 4Pulmonary, Allergy and Critical Care Medicine, Duke University Medical Center, Durham, NC, United States, 5Radiology, Duke University Medical Center, Durham, NC, United States

Synopsis

The use of 129Xe MRI to characterize ventilation has received little attention in IPF because these patients exhibit few ventilation defect regions (VDR) compared to those with other obstructive lung diseases. Here, we evaluate other aspects of the ventilation distribution by optimized linear binning. Ventilation distributions were quantified to provide not only VDR, but also low and high-intensity regions (LIR, HIR). We found that HIR was reduced by 3-fold in patients with late versus early stage disease, as measured by GAP IPF stage. Thus, loss of HIR may be a useful marker of disease progression in IPF.

Purpose

With its ability to assess regional pulmonary gas exchange, hyperpolarized 129Xe MRI may be valuable for both diagnosing and monitoring idiopathic pulmonary fibrosis (IPF) [1]. However, the use of 129Xe MRI to characterize ventilation has received little attention because IPF patients exhibit remarkably few ventilation defect regions (VDR) compared to those with obstructive lung diseases. We have recently developed a linear binning method to quantify ventilation distribution that also reports on low and high-intensity regions (LIR, HIR). The objective of this work was therefore to test whether 129Xe ventilation MRI, quantified in this manner, exhibits features that can differentiate early-stage from later-stage IPF. To do so we compared 129Xe MRI binning with the GAP index [2], which stages IPF using gender, age and physiology.

Methods

129Xe ventilation MRI scans were acquired in 10 young controls (25.7±3.4 yrs) and 10 IPF patients (67.1±7.6 yrs, FVC=66.9±21.4%, and DLCO 49.7±12.1%). MRI used a multi-slice GRE scan: FOV = 40 cm, 12.5 mm slice, matrix = 128×128, BW = 8 kHz, α = 7-10°, TR/TE = 8.9/2.1ms. To enable semi-automated quantification, the thoracic cavity was delineated using a breath-hold 1H FIESTA (SSFP) image: FOV = 40 cm, 12.5 mm slice, matrix = 192×192, α = 45°, TR/TE = 2.8/1.2 ms, BW = 125 kHz. These were registered to the 129Xe MRI using affine transformations. The 129Xe MRI and registered 1H image were segmented by region growing to create a combined mask that included both the thoracic cavity and the airways. This mask was eroded by 1 pixel and vascular structures were removed using Frangi’s vessel-enhancing algorithm. 129Xe images were corrected for B1 inhomogeneity, and then rescaled by the 99th percentile of their cumulative intensity distribution so that the resulting pixel values ranged from 0-1. The distribution in healthy young volunteers had a mean = 0.52 and standard deviation SD = 0.18. These were used to define 6 bins for mapping ventilation distribution, and to quantify defects, low and high-intensity regions as follows: VDR—[0, mean-2SD], LIR—[mean-2SD, mean-1SD], and HIR—[mean+1SD, 1].

Results

In younger controls VDR = 2.6±1.8%, LIR = 17.5±5.7%, HIR = 16.7±3.3%, and thoracic cavity volume was TCV = 3.8±0.6L. By comparison, IPF subjects had a smaller thoracic cavity volume (TCV = 2.9±0.3L), modestly increased VDR (8.9±5.4%), LIR (25.4±9.7%), and HIR (19.2±12.9%). However, HIR varied significantly among IPF patients, and exhibited a significant negative correlation with GAP staging index (r=-0.66, p=0.04). For patients with GAP<2, HIR=29.9±11.7%. By contrast, for patients with GAP>3 HIR decreased to 8.3±3.4%. Thus, in patients with more advanced disease, as characterized by GAP>3, HIR was more than 3-fold lower than in patients with early disease.

Discussion

Although 129Xe gas exchange metrics will likely remain the primary focus in IPF, this study shows that 129Xe ventilation MRI may help in further staging the disease. The dramatic reduction in high-intensity pixels for patients with more advanced disease suggests that the fibrosis progressed sufficiently to compromise lung compliance. By contrast, it appears that earlier in the disease process, there are still pockets of compliant lung that receive proportionally more ventilation. Thus, loss of HIR may be a useful marker of disease progression in IPF.

Acknowledgements

R01HL105643, R01HL126771, P41 EB015897, Gilead Sciences

References

[1] Kaushik SS, et al. Probing the regional distribution of pulmonary gas exchange through single-breath gas- and dissolved-phase 129Xe MR imaging. J Appl Physiol 2013;115:850–601. [2] Kolb M, Collard HR. Staging of idiopathic pulmonary fibrosis: past, present and future. Eur Respir Rev 2014;23:220–4.

Figures

Figure 1 129Xe MRI and associated binning maps for healthy young control, early stage IPF and later stage IPF.



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