TY - JOUR T1 - Dynamic contrast-enhanced magnetic resonance imaging of the lung reveals important pathobiology in idiopathic pulmonary fibrosis JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00907-2020 SP - 00907-2020 AU - Sydney B. Montesi AU - Iris Zhou AU - Lloyd L. Liang AU - Subba R. Digumarthy AU - Sarah Mercaldo AU - Nathaniel Mercaldo AU - Ravi T. Seethamraju AU - Bruce Rosen AU - Peter Caravan Y1 - 2021/01/01 UR - http://openres.ersjournals.com/content/early/2021/07/22/23120541.00907-2020.abstract N2 - Introduction Evidence suggest that abnormalities occur in the lung microvasculature in idiopathic pulmonary fibrosis (IPF). We hypothesized that dynamic contrast-enhanced (DCE)-MRI could detect alterations in permeability, perfusion, and extracellular extravascular volume in idiopathic pulmonary fibrosis thus providing in vivo regional functional information not otherwise available.Methods Healthy controls and IPF subjects underwent DCE-MRI of the thorax using a dynamic volumetric radial sampling sequence and administration of gadoterate meglumine at a dose of 0.1 mmol·kg−1 at 2 mL·s−1. Model-free analysis of signal intensity versus time curves in regions of interest from a lower, middle, and upper axial plane and a posterior coronal plane yielded parameters reflective of perfusion and permeability (peak enhancement and rate of contrast arrival, kwashin) and the extracellular extravascular space (rate of contrast clearance, kwashout). These imaging parameters were compared between IPF and healthy control subjects, and between fast/slow IPF progressors.Results IPF subjects (n=16, M=56%, age=67.5 (range 60–79)) had significantly reduced peak enhancement and slower kwashin in all measured lung regions compared to the healthy volunteers (n=17, M=65%, age=58 (range 51–63)) on unadjusted analyses consistent with microvascular alterations. kwashout, as a measure of the extravascular extracellular space, was significantly slower in the lower lung and posterior coronal regions in the IPF subjects consistent with an increased extravascular extracellular space. All estimates were attenuated after adjusting for age. Similar trends were observed, but only the associations with kwashin remained statistically significant. Among IPF subjects, kwashout rates nearly perfectly discriminated between those with rapidly progressive disease versus those with stable/slowly progressive disease.Conclusions DCE-MRI detects changes in the microvasculature and extravascular extracellular space in IPF thus providing in vivo regional functional information.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. Montesi reports grants from CHEST Foundation, grants from Francis Family Foundation , grants from National Institutes of Health, during the conduct of the study; other from United Therapeutics, other from Merck, other from Promedior , other from Pliant Therapeutics, personal fees from Wolters Kluwer, personal fees from DevPro Biopharma, outside the submitted work.Dr. Montesi reports grants from CHEST Foundation, grants from Francis Family Foundation , grants from National Institutes of Health, during the conduct of the study; other from United Therapeutics, other from Merck, other from Promedior , other from Pliant Therapeutics, personal fees from Wolters Kluwer, personal fees from DevPro Biopharma, outside the submitted work; .Conflict of interest: Dr. Zhou has nothing to disclose.Conflict of interest: Dr. Liang has nothing to disclose.Conflict of interest: S.R. Digumarthy reports acting as an independent image analyst for clinical trials through their hospital for Merck, Pfizer, Bristol Mayer Squibb, Novartis, Roche, Polaris, Cascadian, Abbvie, Gradalis, Clinical Bay and Zai Laboratories; an honorarium from Siemens Medical Solutions; and a research grant from Lunit INC, all outside the submitted work.Conflict of interest: Dr. Mercaldo has nothing to disclose.Conflict of interest: Dr. Mercaldo has nothing to disclose.Conflict of interest: Dr. Seethamraju reports personal fees from Siemens Medical Solutions, USA Inc., outside the submitted work; .Conflict of interest: Dr. Rosen has nothing to disclose.Conflict of interest: Dr. Caravan reports grants from National Institutes of Health, during the conduct of the study; other from Reveal Pharmaceuticals, other from Collagen Medical LLC, grants from Indalo Therapeutics, grants from Pliant Therapeutics, grants from Celgene, grants from Pfizer, grants from Takeda, outside the submitted work; . ER -