Functional xenon-129 magnetic resonance imaging response to antifibrotic treatment in idiopathic pulmonary fibrosis

Abstract

Progression of idiopathic pulmonary fibrosis (IPF) is highly variable [1] and it is clinically challenging to effectively manage care and tailor treatment regimens using antifibrotic medications, such as nintedanib and pirfenidone, on a patient-specific basis [2]. Clinical evaluation of the functional response to these treatments is limited largely to pulmonary function tests (PFTs) (e.g. forced vital capacity (FVC), percentage predicted forced expiratory volume in 1 s (FEV 1 ), diffusing capacity of the lung for carbon monoxide (D LCO ) [3] and/or progression-free survival [4]). The development of more sensitive biomarkers that can provide longitudinal evaluation of regional treatment response would have meaningful clinical utility. Hyperpolarised (HP) xenon-129 ( 129 Xe) magnetic resonance imaging (MRI) has shown potential for evaluating both regional ventilation and gas exchange, with a strong focus on applications in IPF [5][6][7]. Specifically, HP 129 Xe MRI spectroscopy measures of red blood cell (RBC) 129 Xe uptake across the lung tissue and plasma barrier (hereafter "membrane") from the alveolar space, called the RBC-to-membrane ratio, has been shown to be a possible biomarker of future IPF disease progression [8].In this work, we investigate our hypothesis that IPF patients treated with antifibrotic medications will show improved longitudinal trajectories in this candidate biomarker over the course of 1 year. These results have been introduced previously in abstract form [9]. The study was Health Insurance Portability and Accountability Act compliant and informed consent was obtained in accordance with approved institutional review board (UW IRB 2013-0266 and UW IRB 2014-1572) and investigational new drug (United States Food and Drug Administration IND# 118077) protocols. 25 participants with IPF were recruited prospectively, 21 of whom (19 males, mean±SD age 70.1±8.5 years) underwent HP 129 Xe MRI ventilation and spectroscopic imaging at baseline and at 1-year follow-up. Criteria for study inclusion were outpatients aged >18 years with clinical diagnosis of IPF by established means. Potential participants were excluded for any of the following reasons: respiratory illness within 30 days of MRI; oxygen saturation on room air <90%; history of ventricular cardiac arrhythmia; cardiac arrest within the past year; pregnancy; or unable to maintain 15-s breath-hold. All 21 participants underwent treatment for IPF according to the standard of care such that a subgroup was treated with antifibrotic medication ("antifibrotic" group; n=12, 11 males, age 68.1±7.7 years), while the remaining patients were treated with alternative therapies ("no-antifibrotic" group; n=9, eight males, age 72.8±9.2 years). Participants were considered part of the antifibrotic group if they received antifibrotic medication at any point during the study ( pirfenidone: n=8 for full year, n=2 for part of year; nintedanib: n=1 for full year, n=1 for part of year). Patients receiving only partial treatment were medicated as follows: two wer...

Functional gas exchange measures on 129Xe MRI and spectroscopy are associated with age, sex, and BMI in healthy subjects

“…129 Xe gas exchange MRI and spectroscopy are emerging as techniques with clinical potential for evaluating disease status, progression, and therapy response in a range of cardiopulmonary diseases, including asthma ( 1–3 ), COPD ( 4 , 5 ), COVID-19 ( 6 , 7 ), interstitial lung diseases ( 8–11 ), and pulmonary hypertension ( 12–14 ). Inhaled 129 Xe gas freely diffuses from the lung airspaces, through the alveolar-capillary interstitial membrane, and into the capillary bloodstream, where it transiently binds with red blood cells (RBCs).…”

“…Elucidating the contributions of these and other factors to 129 Xe gas exchange measurements is a critical component for differentiating disease processes from expected variation in healthy subjects. Notably, the Mem:Gas and RBC chemical shift 1 Introduction 129 Xe gas exchange MRI and spectroscopy are emerging as techniques with clinical potential for evaluating disease status, progression, and therapy response in a range of cardiopulmonary diseases, including asthma (1-3), COPD (4,5), COVID-19 (6,7), interstitial lung diseases (8)(9)(10)(11), and pulmonary hypertension (12)(13)(14). Inhaled 129 Xe gas freely diffuses from the lung airspaces, through the alveolar-capillary interstitial membrane, and into the capillary bloodstream, where it transiently binds with red blood cells (RBCs).…”