Sean B. Fain

Severe asthma: lessons learned from the National Heart, Lung, and Blood Institute Severe Asthma Research Program.

The National Heart, Lung, and Blood Institute Severe Asthma Research Program (SARP) has characterized over the past 10 years 1,644 patients with asthma, including 583 individuals with severe asthma. SARP collaboration has led to a rapid recruitment of subjects and efficient sharing of samples among participating sites to conduct independent mechanistic investigations of severe asthma. Enrolled SARP subjects underwent detailed clinical, physiologic, genomic, and radiological evaluations. In addition, SARP investigators developed safe procedures for bronchoscopy in participants with asthma, including those with severe disease. SARP studies revealed that severe asthma is a heterogeneous disease with varying molecular, biochemical, and cellular inflammatory features and unique structure-function abnormalities. Priorities for future studies include recruitment of a larger number of subjects with severe asthma, including children, to allow further characterization of anatomic, physiologic, biochemical, and genetic factors related to severe disease in a longitudinal assessment to identify factors that modulate the natural history of severe asthma and provide mechanistic rationale for management strategies.

Optimized 3D ultrashort echo time pulmonary MRI

To optimize 3D radial ultrashort echo time MRI for high resolution whole‐lung imaging.

Lung imaging in asthmatic patients: The picture is clearer

Imaging of the lungs in patients with asthma has evolved dramatically over the last decade with sophisticated techniques, such as computed tomography, magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography. New insights into current and future modalities for imaging in asthmatic patients and their application are discussed to potentially shed a clearer picture of the underlying pathophysiology of asthma, especially severe asthma, and the proposed clinical utility of imaging in patients with this common disease.

Functional imaging of the lungs with gas agents

This review focuses on the state‐of‐the‐art of the three major classes of gas contrast agents used in magnetic resonance imaging (MRI)—hyperpolarized (HP) gas, molecular oxygen, and fluorinated gas—and their application to clinical pulmonary research. During the past several years there has been accelerated development of pulmonary MRI. This has been driven in part by concerns regarding ionizing radiation using multidetector computed tomography (CT). However, MRI also offers capabilities for fast multispectral and functional imaging using gas agents that are not technically feasible with CT. Recent improvements in gradient performance and radial acquisition methods using ultrashort echo time (UTE) have contributed to advances in these functional pulmonary MRI techniques. The relative strengths and weaknesses of the main functional imaging methods and gas agents are compared and applications to measures of ventilation, diffusion, and gas exchange are presented. Functional lung MRI methods using these gas agents are improving our understanding of a wide range of chronic lung diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis in both adults and children. J. Magn. Reson. Imaging 2016;43:295–315.

Pulmonary 3He magnetic resonance imaging of childhood asthma.

BACKGROUNDnMagnetic resonance imaging (MRI) with (3)He does not require ionizing radiation and has been shown to detect regional abnormalities in lung ventilation and structure in adults with asthma, but the method has not been extended to children with asthma. Measurements of regional lung ventilation and microstructure in subjects with childhood asthma could advance our understanding of disease mechanisms.nnnOBJECTIVEnWe sought to determine whether (3)He MRI in children can identify abnormalities related to the diagnosis of asthma or prior history of respiratory illness.nnnMETHODSnForty-four children aged 9 to 10 years were recruited from a birth cohort at increased risk of asthma and allergic diseases. For each subject, a time-resolved 3-dimensional image series and a 3-dimensional diffusion-weighted image were acquired in separate breathing maneuvers. The numbers and sizes of ventilation defects were scored, and regional maps and statistics of average (3)He diffusion lengths were calculated.nnnRESULTSnChildren with mild-to-moderate asthma had lower average root-mean-square diffusion length (X(rms)) values (P = .004), increased regional SD of diffusion length values (P = .03), and higher defect scores (P = .03) than those without asthma. Children with histories of wheezing illness with rhinovirus infection before the third birthday had lower X(rms) values (P = .01) and higher defect scores (P = .05).nnnCONCLUSIONnMRI with (3)He detected more and larger regions of ventilation defect and a greater degree of restricted gas diffusion in children with asthma compared with those seen in children without asthma. These measures are consistent with regional obstruction and smaller and more regionally variable dimensions of the peripheral airways and alveolar spaces.

Quantitative Magnetic Resonance Imaging of Bronchopulmonary Dysplasia in the Neonatal Intensive Care Unit Environment

RATIONALEnBronchopulmonary dysplasia (BPD) is a prevalent yet poorly characterized pulmonary complication of premature birth; the current definition is based solely on oxygen dependence at 36 weeks postmenstrual age without objective measurements of structural abnormalities across disease severity.nnnOBJECTIVESnWe hypothesize that magnetic resonance imaging (MRI) can spatially resolve and quantify the structural abnormalities of the neonatal lung parenchyma associated with premature birth.nnnMETHODSnUsing a unique, small-footprint, 1.5-T MRI scanner within our neonatal intensive care unit (NICU), diagnostic-quality MRIs using commercially available sequences (gradient echo and spin echo) were acquired during quiet breathing in six patients with BPD, six premature patients without diagnosed BPD, and six full-term NICU patients (gestational ages, 23-39 wk) at near term-equivalent age, without administration of sedation or intravenous contrast. Images were scored by a radiologist using a modified Ochiai score, and volumes of high- and low-signal intensity lung parenchyma were quantified by segmentation and threshold analysis.nnnMEASUREMENTS AND MAIN RESULTSnSignal increases, putatively combinations of fibrosis, edema, and atelectasis, were present in all premature infants. Infants with diagnosed BPD had significantly greater volume of high-signal lung (meanu2009±u2009SD, 26.1u2009±u200913.8%) compared with full-term infants (7.3u2009±u20098.2%; Pu2009=u20090.020) and premature infants without BPD (8.2u2009±u20096.4%; Pu2009=u20090.026). Signal decreases, presumably alveolar simplification, only appeared in the most severe BPD cases, although cystic appearance did increase with severity.nnnCONCLUSIONSnPulmonary MRI reveals quantifiable, significant differences between patients with BPD, premature patients without BPD, and full-term control subjects. These methods could be implemented to individually phenotype disease, which may impact clinical care and predict future outcomes.

Oxygen-enhanced 3D radial ultrashort echo time magnetic resonance imaging in the healthy human lung

The purpose of this work was to use 3D radial ultrashort echo time (UTE) MRI to perform whole‐lung oxygen‐enhanced (OE) imaging in humans.

Hyperpolarized Helium-3 MRI of Exercise-Induced Bronchoconstriction During Challenge and Therapy

To investigate the utility of hyperpolarized He‐3 MRI for detecting regional lung ventilated volume (VV) changes in response to exercise challenge and leukotriene inhibitor montelukast, human subjects with exercise induced bronchoconstriction (EIB) were recruited. This condition is described by airway constriction following exercise leading to reduced forced expiratory volume in 1 second (FEV1) coinciding with ventilation defects on hyperpolarized He‐3 MRI.

Exercise-induced bronchoconstriction: reproducibility of hyperpolarized 3He MR imaging.

PURPOSEnTo quantitatively evaluate interday, interreader, and intersite agreement of readers of hyperpolarized helium 3 (HPHe) MR images in patients with exercise-induced bronchoconstriction.nnnMATERIALS AND METHODSnThis HIPAA-compliant, institutional review board approved study included 13 patients with exercise-induced bronchoconstriction. On two separate days, HPHe MR imaging of the lungs was performed at baseline, immediately after a 10-minute exercise challenge (postchallenge), and 45 minutes after exercise (recovery). Patients were imaged at two sites, six at site A and seven at site B. Images were analyzed independently by multiple readers at each site. Lung volume, ventilation defect volume, ventilated volume, and the number of defects were measured quantitatively, and the location of defects was evaluated qualitatively at site A. Interday and interreader agreement were evaluated by using the intraclass correlation coefficient (ICC), and intersite agreement was evaluated by using a modified Bland-Altman analysis.nnnRESULTSnThe ICC between days for ventilation defect volume, ventilated volume, and number of defects was at least 0.74 at both sites. The ICC for lung volume was greater at site B (0.83-0.86) than at site A (0.60-0.65). Defects seen in the same location in the lung on both days included 19.7% of those seen on baseline images and 29.2% and 18.6% of defects on postchallenge and recovery images, respectively. Interreader ICC for each measurement was at least 0.82 for each site. Analysis of intersite agreement showed biases of 612 mL for lung volume, -60.7 mL for ventilation defect volume, 2.91% for ventilated volume, and -6.56 for number of defects.nnnCONCLUSIONnThe reported measures of reproducibility of HPHe MR imaging may help in the design and interpretation of single- and multicenter studies of patients with exercise-induced bronchoconstriction.

Retrospective respiratory self-gating and removal of bulk motion in pulmonary UTE MRI of neonates and adults.

To implement pulmonary three‐dimensional (3D) radial ultrashort echo‐time (UTE) MRI in non‐sedated, free‐breathing neonates and adults with retrospective motion tracking of respiratory and intermittent bulk motion, to obtain diagnostic‐quality, respiratory‐gated images.