Original Article

Magnetic Resonance Elastography (MRE) of Bleomycin-Induced Pulmonary Fibrosis in an Animal Model

Fakhouri, Faisal PhD^∗,†,‡; Joseph, Matthew BS^§; Ballinger, Megan PhD^§,∥; Shukla, Vasudha PhD^∗; Weimar, David BS^§,∥; Novak, Caymen PhD^§,∥; Ghadiali, Samir PhD^∗,∥; Kolipaka, Arunark PhD, FAHA^∗,†

Author Information

From the ^∗Department of Biomedical Engineering, The Ohio State University, Columbus

^†Department of Radiology, The Ohio State University Wexner Medical Center, Columbus

^‡Department of Biomedical Technology, King Saud University, Riyadh, KSA

^§Davis Heart and Lung Research Institute, The Ohio State University, Columbus

^∥Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH.

Received for publication August 15, 2022; and accepted for publication, after revision, September 24, 2022.

Conflicts of interest and sources of funding: NIH-R01HL124096, R01AR075062, R01HL141217, and NCAI-18-11 and the President's Accelerator Award by The Ohio State University.

Correspondence to: Arunark Kolipaka, PhD, FAHA, 395 W 12th Ave, 4th Floor, Columbus, OH 43210. E-mail: [email protected].

Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.investigativeradiology.com).

Investigative Radiology 58(4):p 299-306, April 2023. | DOI: 10.1097/RLI.0000000000000935

Abstract

Background

Idiopathic pulmonary fibrosis is responsible for 40,000 deaths annually in the United States. A hallmark of idiopathic pulmonary fibrosis is elevated collagen deposition, which alters lung stiffness. Clinically relevant ways to measure changes in lung stiffness during pulmonary fibrosis are not available, and new noninvasive imaging methods are needed to measure changes in lung mechanical properties.

Objectives

Magnetic resonance elastography (MRE) is an in vivo magnetic resonance imaging technique proven to detect changes in shear stiffness in different organs. This study used MRE, histology, and bronchoalveolar lavage (BAL) to study changes in the mechanical and structural properties of the lungs after bleomycin-induced pulmonary fibrosis in pigs.

Materials and Methods

Pulmonary fibrosis was induced in 9 Yorkshire pigs by intratracheal instillation of 2 doses of bleomycin into the right lung only. Magnetic resonance elastography scans were performed at baseline and week 4 and week 8 postsurgery in a 1.5 T magnetic resonance imaging scanner using a spin-echo echo planar imaging sequence to measure changes in lung shear stiffness. At the time of each scan, a BAL was performed. After the final scan, whole lung tissue was removed and analyzed for histological changes.

Results

Mean MRE-derived stiffness measurements at baseline, week 4, and week 8 for the control (left) lungs were 1.02 ± 0.27 kPa, 0.86 ± 0.29 kPa, and 0.68 ± 0.20 kPa, respectively. The ratio of the shear stiffness in the injured (right) lung to the uninjured control (left) lung at baseline, week 4, and week 8 was 0.98 ± 0.23, 1.52 ± 0.41, and 1.64 ± 0.40, respectively. High-dose animals showed increased protein in BAL fluid, elevated inflammation observed by the presence of patchy filtrates, and enhanced collagen and α-smooth muscle actin staining on histological sections. Low-dose animals and the control (left) lungs of high-dose animals did not show significant histopathological changes.

Conclusion

This study demonstrated that MRE can be used to detect changes in lung stiffness in pigs after bleomycin challenge.

Article Keywords

Keywords
magnetic resonance elastography, MR elastography of the lung, pulmonary fibrosis, pulmonary fibrosis lung stiffness, bleomycin animal model, bleomycin pig model

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Magnetic Resonance Elastography (MRE) of Bleomycin-Induced Pulmonary Fibrosis in an Animal Model