Assessing Functional Changes in Lungs with Idiopathic Pulmonary Fibrosis using Hyperpolarized Xenon-129 MRI
Kun Qing1, Borna Mehrad1, John P. Mugler, III1, Kai Ruppert1,2, Jaime F. Mata1, Nicholas J. Tustison1, Steven Guan1, Y. Michael Shim1, Iulian C. Ruset3, F. William Hersman3,4, and Talissa A. Altes1,5

1University of Virginia, Charlottesville, VA, United States, 2Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, 3Xemed LLC, Durham, NH, United States, 4University of New Hampshire, Durham, NH, United States, 5University of Missouri, Columbia, MO, United States

Synopsis

Idiopathic pulmonary fibrosis (IPF) is a fatal disease leading to 40,000 deaths each year in the US. Current clinical tools are remarkably limited in their ability to discriminate between subsets of IPF patients. In this study, we demonstrated the ability of a recently developed imaging tool, hyperpolarized xenon-129 MRI, to detect pulmonary physiology highly relevant to pathology found in IPF with 3-D resolution. Xenon-129 MRI may represent a novel tool that can detect previously unrecognized subsets of patients with IPF relevant to treatment and prognosis of this disease.

Introduction

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that culminates in death from respiratory failure a median of 3 years after diagnosis, and that causes 40,000 deaths each year in the US [1, 2]. A key challenge in the care of IPF patients is that the natural history of the illness is unpredictable, with some patients having frequent exacerbations in quick succession leading to rapid deterioration and death, while others have a more benign course with few or no exacerbations [3]. Current clinical tools, including chest CT, pulmonary function tests (PFTs), and lung biopsy are remarkably limited in their ability to discriminate between subsets of IPF patients and correlate with disease prognosis. Hyperpolarized xenon-129 (Xe129) MRI is a powerful, recently-developed technology that provides regional and quantitative information about regional lung ventilation, gas uptake (exchange) and perfusion [4], but has not been studied in IPF to date.

Purpose

To test the ability of hyperpolarized xenon-129 MRI to detect changes of lung physiology in subjects with IPF.

Methods

Seven patients with IPF (age 66±15) and 10 age-matched healthy controls (age 58±14) underwent PFTs including spirometry and diffusion capacity (DLCO), and hyperpolarized xenon-129 MRI including 3-D ventilation (resolution: 4x4x15 mm3) and dissolved-phase (Xe129 DP) imaging (resolution 7.6x7.6x17.6 mm3) [4]. Four metrics were generated from the Xe129 MRI, including measurement of airflow obstruction: percent ventilation defects (Vdef%) [5], and three measurements of gas uptake into lung tissue and blood: tissue-to-gas, RBC-to-gas, and RBC-to-tissue ratios [4]. Mann-Whitney U test was used to compare the PFT and MRI data acquired from the IPF and control groups.

Results and Discussion

As compared to controls, patients with IPF had significantly lower FEV1 %pred (IPF: 68±19%, control: 112±13%, p<0.001), FVC %pred (IPF: 67±19%, control: 121±29%, p<0.001) and DLCO/Va %pred (IPF: 75±18%, control: 93±14%, p=0.04), but higher FEV1/FVC (IPF: 0.82±0.04, control: 0.77±0.06, p=0.026). On xenon-129 MRI, IPF patients had ventilation defects close to those from controls (IPF: 31±11%, control: 21±9%, p=0.041; Fig. 1, right column). In contrast, the measured gas exchange from lung parenchyma to blood was significantly lower in subjects with IPF (RBC-to-tissue ratio: IPF: 0.19±0.05, control: 0.28±0.05, p=0.002; Fig. 1, middle column). Interestingly, the gas uptake by tissue was significantly higher in IPF compared to healthy subjects (tissue-to-gas ratio: IPF: 1.41±0.14%, control: 1.10±0.17%, p=0.005; Fig. 1, left column), a finding that may be attributable to septal wall thickening due to pulmonary fibrosis or inflammation. In addition, IPF patients showed marked regional heterogeneity in the tissue-to-gas ratio maps, with the lower lobes and periphery of the lungs having higher tissue-to-gas ratios than the upper lobes and central regions (an example shown in Fig. 2). This is consistent with existing findings that IPF is a disease of the basal and peripheral lungs that progresses centrally and toward the lung apices over time [6].

Conclusion

We have demonstrated the ability of hyperpolarized xenon-129 MRI to detect pulmonary physiology highly relevant to pathology found in IPF with 3-D resolution. Hyperpolarized xenon-129 MRI may be able to identify previously unrecognized subsets of patients with IPF that may be relevant to treatment and prognosis of this disease.

Acknowledgements

This work was supported by a Transformative, Collaborative Science Pilot Grant from University of Virginia School of Medicine and NIH R01 HL109618.

References

[1] Flaherty, K.R., et al. Am J Respir Crit Care Med, 2001. 164(9): p. 1722-7. [2] Nicholson, A.G., et al. Am J Respir Crit Care Med, 2000. 162(6): p. 2213-7. [3] Collard, H.R., et al. Am J Respir Crit Care Med, 2007. 176(7): p. 636-43. [4] Qing, K., et al. J Magn Reson Imaging, 2014. 39(2): p. 346-59. [5] Tustison NJ, et al. J. Magn. Reson. Imaging, 2011. 34(4): p. 831-841. [6] Travis, W.D., et al. Am J Respir Crit Care Med, 2013. 188(6): p. 733-48.

Figures

Figure 1. Boxplots of the whole-lung Xe129 tissue-to-gas, RBC-to-tissue ratios and Vdef% from 10 age-matched normal subjects and 7 subjects with IPF. Subjects with IPF had significantly higher tissue-to-gas ratios (1.41±0.14%; p=0.005) and lower RBC-to-tissue ratios (0.19±0.05; p=0.002) as compared to the healthy subjects (tissue-to-gas: 1.10±0.17%; RBC-to-tissue: 0.28±0.05). The measured Vdef% from the two groups had substantial overlap (IPF: 31±11%, healthy: 21±9%, p=0.041).

Figure 2. Hyperpolarized xenon-129 tissue-to-gas and RBC-to-tissue ratio maps (a single coronal slice from 3-D image sets) acquired from one healthy volunteer (age 52, Female) and a patient with IPF (age 73, Male).



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