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1.
Respir Med ; 180: 106368, 2021.
Article in English | MEDLINE | ID: mdl-33740737

ABSTRACT

INTRODUCTION: Pulmonary function tests (PFTs) are the main objective measures used to assess asthma in children. However, PFTs provide a global measure of lung function. Hyperpolarised xenon-129 magnetic resonance imaging (129Xe-MRI) can assess lung function spatially. This cross-sectional cohort study aimed to evaluate the use of 129Xe-MRI in detecting ventilation abnormalities in children with well-controlled severe asthma pre- and post-bronchodilator (BD). METHOD: Six healthy children (aged 11 ± 3) and six with well-controlled severe asthma (14 ± 1) underwent spirometry, multiple breath washout (MBW), and 129Xe-MRI. These tests were repeated post-BD in the asthma cohort. Image analysis was performed in MATLAB. Wilcoxon signed-rank test, repeated measures analysis of variance (ANOVA), and Spearman's rank correlation coefficient were used for statistical analysis. RESULTS: A significantly higher number of ventilation defects were found in the asthma cohort pre-BD compared to the healthy participants and post-BD within the asthma cohort (p = 0.02 and 0.01). A greater number of wedge-shaped defects were detected in the asthma cohort pre-BD compared to healthy participants and post-BD within the asthma cohort (p = 0.01 and 0.008, respectively). 129Xe ventilation defect percentage (VDP) and coefficient of variation (CoV) were significantly higher in the asthma cohort pre-BD compared to the healthy cohort (p = 0.006 for both). VDP and CoV were reduced significantly post-BD in the asthma cohort, to a level where there was no longer a significant difference between the two cohorts. CONCLUSION: 129Xe-MRI is a sensitive marker of ventilation inhomogeneity in paediatric severe asthma and may potentially be used as a biomarker to assess disease progression and therapeutic response.


Subject(s)
Albuterol/therapeutic use , Asthma/diagnosis , Forced Expiratory Volume/drug effects , Lung/diagnostic imaging , Magnetic Resonance Imaging/methods , Xenon Isotopes/pharmacology , Adolescent , Asthma/drug therapy , Asthma/physiopathology , Bronchodilator Agents/therapeutic use , Child , Cross-Sectional Studies , Female , Humans , Lung/physiopathology , Male , Pilot Projects
2.
Sci Rep ; 10(1): 7385, 2020 04 30.
Article in English | MEDLINE | ID: mdl-32355256

ABSTRACT

Hyperpolarized 129Xe magnetic resonance imaging (MRI) is capable of regional mapping of pulmonary gas-exchange and has found application in a wide range of pulmonary disorders in humans and animal model analogs. This study is the first application of 129Xe MRI to the monocrotaline rat model of pulmonary hypertension. Such models of preclinical pulmonary hypertension, a disease of the pulmonary vasculature that results in right heart failure and death, are usually assessed with invasive procedures such as right heart catheterization and histopathology. The work here adapted from protocols from clinical 129Xe MRI to enable preclinical imaging of rat models of pulmonary hypertension on a Bruker 7 T scanner. 129Xe spectroscopy and gas-exchange imaging showed reduced 129Xe uptake by red blood cells early in the progression of the disease, and at a later time point was accompanied by increased uptake by barrier tissues, edema, and ventilation defects-all of which are salient characteristics of the monocrotaline model. Imaging results were validated by H&E histology, which showed evidence of remodeling of arterioles. This proof-of-concept study has demonstrated that hyperpolarized 129Xe MRI has strong potential to be used to non-invasively monitor the progression of pulmonary hypertension in preclinical models and potentially to also assess response to therapy.


Subject(s)
Hypertension, Pulmonary , Lung , Magnetic Resonance Imaging , Pulmonary Gas Exchange , Xenon Isotopes/pharmacology , Animals , Disease Models, Animal , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/metabolism , Hypertension, Pulmonary/physiopathology , Lung/metabolism , Lung/physiopathology , Male , Rats , Rats, Sprague-Dawley
3.
Sci Rep ; 9(1): 2413, 2019 02 20.
Article in English | MEDLINE | ID: mdl-30787357

ABSTRACT

While hyperpolarized xenon-129 (HXe) MRI offers a wide array of tools for assessing functional aspects of the lung, existing techniques provide only limited quantitative information about the impact of an observed pathology on overall lung function. By selectively destroying the alveolar HXe gas phase magnetization in a volume of interest and monitoring the subsequent decrease in the signal from xenon dissolved in the blood inside the left ventricle of the heart, it is possible to directly measure the contribution of that saturated lung volume to the gas transport capacity of the entire lung. In mechanically ventilated rabbits, we found that both xenon gas transport and transport efficiency exhibited a gravitation-induced anterior-to-posterior gradient that disappeared or reversed direction, respectively, when the animal was turned from supine to prone position. Further, posterior ventilation defects secondary to acute lung injury could be re-inflated by applying positive end expiratory pressure, although at the expense of decreased gas transport efficiency in the anterior volumes. These findings suggest that our technique might prove highly valuable for evaluating lung transplants and lung resections, and could improve our understanding of optimal mechanical ventilator settings in acute lung injury.


Subject(s)
Gases/metabolism , Heart/physiology , Lung/metabolism , Pulmonary Gas Exchange/physiology , Animals , Heart Ventricles/drug effects , Humans , Lung/physiology , Magnetic Resonance Imaging/methods , Prone Position , Rabbits , Respiration, Artificial , Ventricular Function/physiology , Xenon Isotopes/pharmacology
4.
Methods Enzymol ; 602: 249-272, 2018.
Article in English | MEDLINE | ID: mdl-29588032

ABSTRACT

The physiological activity of xenon has long been recognized, though the exact nature of its interactions with biomolecules remains poorly understood. Xe is an inert noble gas, but can act as a general anesthetic, most likely by binding internal hydrophobic cavities within proteins. Understanding Xe-protein interactions, therefore, can provide crucial insight regarding the mechanism of Xe anesthesia and potentially other general anesthetic agents. Historically, Xe-protein interactions have been studied primarily through X-ray crystallography and nuclear magnetic resonance (NMR). In this chapter, we first describe our methods for preparing Xe derivatives of protein crystals and identifying Xe-binding sites. Second, we detail our procedure for 129Xe hyper-CEST NMR spectroscopy, a versatile NMR technique well suited for characterizing the weak, transient nature of Xe-protein interactions.


Subject(s)
Anesthetics, Inhalation/pharmacology , Myoglobin/metabolism , Nuclear Magnetic Resonance, Biomolecular/methods , Xenon Isotopes/pharmacology , Anesthetics, Inhalation/chemistry , Binding Sites , Crystallography, X-Ray , Hydrophobic and Hydrophilic Interactions , Myoglobin/chemistry , Xenon Isotopes/chemistry
5.
J Cyst Fibros ; 16(2): 275-282, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27477942

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a genetic disease which carries high morbidity and mortality from lung-function decline. Monitoring disease progression and treatment response in young patients is desirable, but serial imaging via CT is often considered prohibitive, and detailed functional information cannot be obtained using conventional imaging techniques. Hyperpolarized 129Xe magnetic resonance imaging (MRI) can depict and quantify regional ventilation, but has not been investigated in pediatrics. We hypothesized that 129Xe MRI is feasible and would demonstrate ventilation defects in mild CF lung disease with greater sensitivity than FEV1. METHODS: 11 healthy controls (age 6-16years) and 11 patients with mild CF (age 8-16years, Forced Expiratory Volume (FEV1) percent predicted >70%) were recruited for this study. Nine CF patients had an FEV1>85%. Each subject was imaged via hyperpolarized 129Xe MRI, and the ventilation defect percentage (VDP) was measured. FEV1 and VDP were compared between the groups. RESULTS: FEV1 for controls was 100.3%±8.5% (mean±sd) and for CF patients was 97.9%±16.0% (p=0.67). VDP was 6.4%±2.8% for controls and 18.3%±8.6% for CF (p<0.001). When considering the 9 CF patients with normal FEV1 (>85%), the mean FEV1 was 103.1%±12.3% (p=0.57 compared to controls) and VDP was 15.4%±6.3% (p=0.002). CONCLUSIONS: Hyperpolarized 129Xe MRI demonstrated ventilation defects in CF patients with normal FEV1 and more effectively discriminated CF from controls than FEV1. Thus 129Xe may be a useful outcome measure to detect mild CF lung disease, to investigate regional lung function in pediatric lung diseases, and to follow disease progression.


Subject(s)
Cystic Fibrosis , Magnetic Resonance Imaging/methods , Xenon Isotopes/pharmacology , Adolescent , Child , Cystic Fibrosis/diagnosis , Cystic Fibrosis/physiopathology , Disease Progression , Female , Forced Expiratory Volume , Humans , Male , Predictive Value of Tests , Pulmonary Ventilation , Respiratory Function Tests/methods , Sensitivity and Specificity
6.
Vestn Ross Akad Med Nauk ; (9): 32-7, 2003.
Article in Russian | MEDLINE | ID: mdl-14598734

ABSTRACT

Xenon (Xe) is being more widely used in medicine owing to its unique physical-and-chemical properties of a noble gas. However, the knowledge about the physiological and patho-physiological changes occurring in the organism and in its separate structures during the interaction with Xe is still scanty. The aim of this survey was to briefly describe the presently known Xe biological-and-medical properties and certain mechanisms of Xe impact produced on cells and receptors as well as on the release of mediators and hormones. Besides, the Xe hemodynamic effects are also defined. The conclusion is that the Xe effect can be of a complex nature and can depend on the conditions of the body vital activity (optimal condition, activation, lesion), which predetermine, in their turn, the performance of the structural-and-functional units of various cellular systems.


Subject(s)
Anesthetics, Inhalation/pharmacology , Xenon/pharmacology , Adrenal Glands/drug effects , Animals , Brain/drug effects , Cats , Cell Membrane/drug effects , Cells/drug effects , Cells, Cultured , Hemodynamics/drug effects , Hippocampus/drug effects , Humans , Immune System/drug effects , Liver/drug effects , Mice , Mice, Inbred BALB C , Microcirculation/drug effects , Norepinephrine/blood , Patch-Clamp Techniques , Prolactin/blood , Rats , Receptors, Glutamate/drug effects , Receptors, N-Methyl-D-Aspartate/drug effects , Receptors, Neurotransmitter/drug effects , Xenon Isotopes/pharmacology , Xenopus
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