Same-Day Repeatability and 28-Day Reproducibility of Xenon MRI Ventilation in Children With Cystic Fibrosis in a Multi-Site Trial.

Background: MRI with xenon-129 gas (Xe MRI) can assess airflow obstruction and heterogeneity in lung diseases. Specifically, Xe MRI may represent a sensitive modality for future therapeutic trials of cystic fibrosis (CF) therapies. The reproducibility of Xe MRI has not yet been assessed in the context of a multi-site study.

Estimates of primary ciliary dyskinesia prevalence: a scoping review.

Background: Primary ciliary dyskinesia (PCD) is a rare multisystem genetic disease caused by dysfunctional motile cilia. Despite PCD being the second most common inherited airway disease after cystic fibrosis, PCD continues to be under-recognised globally owing to nonspecific clinical features and the lack of a gold standard diagnostic test. Commonly repeated prevalence estimates range from one in 10 000 to one in 20 000, based on regional epidemiological studies with known limitations.

Phase-Resolved Functional Lung (PREFUL) MRI to Quantify Ventilation: Feasibility and Physiological Relevance in Severe Asthma.

Rationale And Objectives: Emergent evidence in several respiratory diseases supports translational potential for Phase-Resolved Functional Lung (PREFUL) MRI to spatially quantify ventilation but its feasibility and physiological relevance have not been demonstrated in patients with asthma. This study compares PREFUL-derived ventilation defect percent (VDP) in severe asthma patients to healthy controls and measures its responsiveness to bronchodilator therapy and relation to established measures of airways disease.

Materials And Methods: Forty-one adults with severe asthma and seven healthy controls performed same-day free-breathing H MRI, Xe MRI, spirometry, and oscillometry.

Beyond Spirometry: Linking Wasted Ventilation to Exertional Dyspnea in the Initial Stages of COPD.

Exertional dyspnea, a key complaint of patients with chronic obstructive pulmonary disease (COPD), ultimately reflects an increased inspiratory neural drive to breathe. In non-hypoxemic patients with largely preserved lung mechanics - as those in the initial stages of the disease - the heightened inspiratory neural drive is strongly associated with an exaggerated ventilatory response to metabolic demand. Several lines of evidence indicate that the so-called excess ventilation (high ventilation-CO output relationship) primarily reflects poor gas exchange efficiency, namely increased physiological dead space.

Semiautomated Segmentation and Analysis of Airway Lumen in Pediatric Patients Using Ultra Short Echo Time MRI.

Rationale And Objectives: Ultra short echo time (UTE) magnetic resonance imaging (MRI) pulse sequences have shown promise for airway assessment, but the feasibility and repeatability in the pediatric lung are unknown. The purpose of this work was to develop a semiautomated UTE MRI airway segmentation pipeline from the trachea-to-tertiary airways in pediatric participants and assess repeatability and lumen diameter correlations to lung function.

Materials And Methods: A total of 29 participants (n = 7 healthy, n = 11 cystic fibrosis, n = 6 asthma, and n = 5 ex-preterm), aged 7-18 years, were imaged using a 3D stack-of-spirals UTE examination at 3 T.

The argument for utilising magnetic resonance imaging as a tool for monitoring lung structure and function in pediatric patients.

Introduction: Although historically challenging to perform in the lung, technological advancements have made Magnetic Resonance Imaging (MRI) increasingly applicable for pediatric pulmonary imaging. Furthermore, a wide array of functional imaging techniques has become available that may be leveraged alongside structural imaging for increasingly sensitive biomarkers, or as outcome measures in the evaluation of novel therapies.

Areas Covered: In this review, recent technical advancements and modern methodologies for structural and functional lung MRI are described.

L-citrulline attenuates lipopolysaccharide-induced inflammatory lung injury in neonatal rats.

Background: Prenatal or postnatal lung inflammation and oxidative stress disrupt alveolo-vascular development leading to bronchopulmonary dysplasia (BPD) with and without pulmonary hypertension. L-citrulline (L-CIT), a nonessential amino acid, alleviates inflammatory and hyperoxic lung injury in preclinical models of BPD. L-CIT modulates signaling pathways mediating inflammation, oxidative stress, and mitochondrial biogenesis-processes operative in the development of BPD.

Intra- and Inter-visit Repeatability of Xenon Multiple-Breath Washout MRI in Children With Stable Cystic Fibrosis Lung Disease.

Background: Multiple-breath washout (MBW) Xe MRI (MBW Xe-MRI) is a promising technique for following pediatric cystic fibrosis (CF) lung disease progression. However, its repeatability in stable CF needs to be established to use it as an outcome measure for novel therapies.

Purpose: To assess intravisit and intervisit repeatability of MBW Xe-MRI in healthy and CF children.

Physical activity levels, pulmonary function, and MRI in children born extremely preterm: A comparison between children with and without bronchopulmonary dysplasia.

Introduction: Children with a history of bronchopulmonary dysplasia (BPD) may have lower physical activity levels, but evidence to date is mixed. This study compared physical activity levels between children born extremely preterm with and without history of BPD, and examined their associations with pulmonary magnetic resonance imaging (MRI) and pulmonary function test (PFT) indices.

Methods: This multicentre cross-sectional study included children aged 7-9 years born extremely preterm, with and without BPD.

Postacute COVID-19 Syndrome: Xe MRI Ventilation Defects and Respiratory Outcomes 1 Year Later.

Background In individuals with postacute COVID-19 syndrome (PACS) and normal pulmonary function, xenon 129 (Xe) MRI ventilation defects, abnormal quality-of-life scores, and exercise limitation were reported 3 months after infection; the longitudinal trajectory remains unclear. Purpose To measure and compare pulmonary function, exercise capacity, quality of life, and Xe MRI ventilation defect percent (VDP) in individuals with PACS evaluated 3 and 15 months after COVID-19 infection. Materials and Methods In this prospective study, participants with PACS aged 18-80 years were enrolled between July 2020 and August 2021 from two quaternary care centers.

Inter- and intravisit repeatability of free-breathing MRI in pediatric cystic fibrosis lung disease.

Purpose: The purpose of this study is to assess the intra- and interscan repeatability of free-breathing phase-resolved functional lung (PREFUL) MRI in stable pediatric cystic fibrosis (CF) lung disease in comparison to static breath-hold hyperpolarized 129-xenon MRI (Xe-MRI) and pulmonary function tests.

Methods: Free-breathing 1-hydrogen MRI and Xe-MRI were acquired from 15 stable pediatric CF patients and seven healthy age-matched participants on two visits, 1 month apart. Same-visit MRI scans were also performed on a subgroup of the CF patients.

A 3D stack-of-spirals approach for rapid hyperpolarized Xe ventilation mapping in pediatric cystic fibrosis lung disease.

Purpose: To demonstrate the feasibility of a rapid 3D stack-of-spirals (3D-SoS) imaging acquisition for hyperpolarized Xe ventilation mapping in healthy pediatric participants and pediatric cystic fibrosis (CF) participants, in comparison to conventional Cartesian multislice (2D) gradient-recalled echo (GRE) imaging.

Methods: The 2D-GRE and 3D-SoS acquisitions were performed in 13 pediatric participants (5 healthy, 8 CF) during separate breath-holds. Images from both sequences were compared on the basis of ventilation defect percent (VDP) and other measures of image similarity.

Persistent Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-acute COVID-19 Syndrome.

Background: In patients with post-acute COVID-19 syndrome (PACS), abnormal gas-transfer and pulmonary vascular density have been reported, but such findings have not been related to each other or to symptoms and exercise limitation. The pathophysiologic drivers of PACS in patients previously infected with COVID-19 who were admitted to in-patient treatment in hospital (or ever-hospitalized patients) and never-hospitalized patients are not well understood.

Purpose: To determine the relationship of persistent symptoms and exercise limitation with xenon 129 (Xe) MRI and CT pulmonary vascular measurements in individuals with PACS.

Xe MRI ventilation defects in ever-hospitalised and never-hospitalised people with post-acute COVID-19 syndrome.

Background: Patients often report persistent symptoms beyond the acute infectious phase of COVID-19. Hyperpolarised Xe MRI provides a way to directly measure airway functional abnormalities; the clinical relevance of Xe MRI ventilation defects in ever-hospitalised and never-hospitalised patients who had COVID-19 has not been ascertained. It remains unclear if persistent symptoms beyond the infectious phase are related to small airways disease and ventilation heterogeneity.

V̇/Q̇ Mismatch: A Novel Target for COPD Treatment.

In people with COPD, pulmonary gas-exchange efficiency may be impaired because of abnormal alveolar ventilation (V˙A), capillary perfusion (Q˙c), or both. Both have been reported in early and mild stages of the disease. Such derangements often accompany significant clinical consequences such as activity-related dyspnea and exercise intolerance.

Clinical Feasibility of Structural and Functional MRI in Free-Breathing Neonates and Infants.

Background: Evaluation of structural lung abnormalities with magnetic resonance imaging (MRI) has previously been shown to be predictive of clinical neonatal outcomes in preterm birth. MRI during free-breathing with phase-resolved functional lung (PREFUL) may allow for complimentary functional information without exogenous contrast.

Purpose: To investigate the feasibility of structural and functional pulmonary MRI in a cohort of neonates and infants with no cardiorespiratory disease.

Application of a 2D frequency encoding sectoral approach to hyperpolarized Xe MRI at low field.

Inhaled hyperpolarized Xe MRI is a non-invasive and radiation risk free lung imaging method, which can directly measure the business unit of the lung where gas exchange occurs: the alveoli and acinar ducts (lung function). Currently, three imaging approaches have been demonstrated to be useful for hyperpolarized Xe MR in lungs: Fast Gradient Recalled Echo (FGRE), Radial Projection Reconstruction (PR), and spiral/cones. Typically, non-Cartesian acquisitions such as PR and spiral/cones require specific data post-processing, such as interpolating, regridding, and density-weighting procedures for image reconstruction, which often leads to smoothing effects and resolution degradation.

Pulmonary Magnetic Resonance Imaging of Ex-Preterm Children with and without Bronchopulmonary Dysplasia.

Children born prematurely, particularly those with bronchopulmonary dysplasia, have persisting lung abnormalities requiring longitudinal monitoring. Pulmonary ultrashort echo time magnetic resonance imaging (MRI) measurements may provide sensitive markers of persisting lung abnormalities and have not been evaluated in school-aged children born prematurely. To compare pulmonary MRI and pulmonary function test measurements in preterm-born school-aged children with and without bronchopulmonary dysplasia.

Hyperpolarized Xe MRI of the rat brain with chemical shift saturation recovery and spiral-IDEAL readout.

Purpose: To demonstrate the feasibility of Xe chemical shift saturation recovery (CSSR) combined with spiral-IDEAL imaging for simultaneous measurement of the time-course of red blood cell (RBC) and brain tissue signals in the rat brain.

Methods: Images of both the RBC and brain tissue Xe signals from the brains of five rats were obtained using interleaved spiral-IDEAL imaging following chemical shift saturation pulses applied at multiple CSSR delay times, τ. A linear fit of the signals to τ was used to calculate the slope of the signal for both RBC and brain tissue compartments on a voxel-by-voxel basis.

Protocols for multi-site trials using hyperpolarized Xe MRI for imaging of ventilation, alveolar-airspace size, and gas exchange: A position paper from the Xe MRI clinical trials consortium.

Hyperpolarized (HP) Xe MRI uniquely images pulmonary ventilation, gas exchange, and terminal airway morphology rapidly and safely, providing novel information not possible using conventional imaging modalities or pulmonary function tests. As such, there is mounting interest in expanding the use of biomarkers derived from HP Xe MRI as outcome measures in multi-site clinical trials across a range of pulmonary disorders. Until recently, HP Xe MRI techniques have been developed largely independently at a limited number of academic centers, without harmonizing acquisition strategies.

Hyperpolarized Xe magnetic resonance spectroscopy in a rat model of bronchopulmonary dysplasia.

Premature infants often require mechanical ventilation and oxygen therapy, which can result in bronchopulmonary dysplasia (BPD), characterized by developmental arrest and impaired lung function. Conventional clinical methods for assessing the prenatal lung are not adequate for the detection and assessment of long-term health risks in infants with BPD, highlighting the need for a noninvasive tool for the characterization of lung microstructure and function. Theoretical diffusion models, like the model of xenon exchange (MOXE), interrogate alveolar gas exchange by predicting the uptake of inert hyperpolarized (HP) Xe gas measured with HP Xe magnetic resonance spectroscopy (MRS).