Correlation of vascular leak measured using gadofosveset-enhanced lung magnetic resonance imaging with radiographic and physiologic measures of fibrosis in patients with idiopathic pulmonary fibrosis
Liang, Lloyd L.
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Idiopathic pulmonary fibrosis (IPF) is an irreversible disease of unknown etiology that involves progressive scarring of the lung tissue, leading to respiratory failure and death.1 IPF is thought to develop from repetitive lung injury and aberrant wound healing that leads to the generation of fibrous tissue rather than restoration of normal tissue.2 It has been suggested in mice that vascular leak after lung injury contributes to the development of lung fibrosis.2,3 Gadofosveset is an intravascular enhancing, gadolinium-based contrast agent used with magnetic resonance imaging (MRI) to assess a variety of biological processes in vivo because it can reversibly bind to albumin.13-14 Gadofosveset has been used to assess endothelial permeability and function, as it diffuses through the vessel walls via leaky neovessels and damaged endothelium.15 Our research group has developed a new method to assess disease activity in IPF patients using gadofosveset-enhanced lung MRI. In unpublished work, we have demonstrated that this technique can be used to generate an albumin extravasation index (AEI), and we have found that this is significantly and diffusely increased in the lung of patients with idiopathic pulmonary fibrosis compared to healthy controls.16 The AEI is a measure of the change in signal intensity post-contrast minus pre-contrast in predefined regions of interest (ROIs) in the lung parenchyma divided by post- minus pre-contrast signal intensity in the ROI in the aorta. In this study, we compared the AEI in patients with IPF to healthy control (HC) subjects and evaluated the correlation between the AEI and high-resolution computed tomography (HRCT) and pulmonary function testing (PFT). We found that IPF subjects had increased AEI values compared with HC subjects. While not statistically significant, AEI was more strongly correlated with fibrosis (interstitial abnormalities) than ground-glass (alveolar abnormalities) on HRCT. Furthermore, there was a possible correlation between AEI and change in percent predicted forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and diffusion capacity of carbon monoxide adjusted for hemoglobin (DLCO) [Hb]. Our results demonstrate that AEI calculations from gadofosveset-enhanced lung MRI are a surrogate measure of vascular leak and can potentially serve as an alternative method for predicting the clinical course and severity of IPF through its correlation with fibrosis on HRCT and pulmonary function.