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Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma.

ABSTRACT: PURPOSE:Asthma is a disease of increasing worldwide importance that calls for new investigative methods. Ex vivo lung tissue is being increasingly used to study functional respiratory parameters independent of confounding systemic considerations but also to reduce animal numbers and associated research costs. In this work, a straightforward laboratory method is advanced to probe dynamic changes in gas inhalation patterns by using an ex vivo small animal ovalbumin (OVA) model of human asthma. METHODS:Hyperpolarized (hp) (129) Xe was actively inhaled by the excised lungs exposed to a constant pressure differential that mimicked negative pleural cavity pressure. The method enabled hp (129) Xe MRI of airway responsiveness to intravenous methacholine (MCh) and airway challenge reversal through salbutamol. RESULTS:Significant differences were demonstrated between control and OVA challenged animals on global lung hp (129) Xe gas inhalation with P?

SUBMITTER: Lilburn DM

PROVIDER: S-EPMC5026173 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma.

Lilburn David M L DM Tatler Amanda L AL Six Joseph S JS Lesbats Clémentine C Habgood Anthony A Porte Joanne J Hughes-Riley Theodore T Shaw Dominick E DE Jenkins Gisli G Meersmann Thomas T

Magnetic resonance in medicine 20151028 4

<h4>Purpose</h4>Asthma is a disease of increasing worldwide importance that calls for new investigative methods. Ex vivo lung tissue is being increasingly used to study functional respiratory parameters independent of confounding systemic considerations but also to reduce animal numbers and associated research costs. In this work, a straightforward laboratory method is advanced to probe dynamic changes in gas inhalation patterns by using an ex vivo small animal ovalbumin (OVA) model of human ast ...[more]

PMID: 26507239

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Project description:PURPOSE:To derive lobar ventilation in patients with chronic obstructive pulmonary disease (COPD) using a rapid time-series hyperpolarized xenon-129 (HPX) magnetic resonance imaging (MRI) technique and compare this to ventilation/perfusion single-photon emission computed tomography (V/Q-SPECT), correlating the results with high-resolution computed tomography (CT) and pulmonary function tests (PFTs). MATERIALS AND METHODS:Twelve COPD subjects (GOLD stages I-IV) participated in this study and underwent HPX-MRI, V/Q-SPECT/CT, high-resolution CT, and PFTs. HPX-MRI was performed using a novel time-series spiral k-space sampling approach. Relative percentage ventilations were calculated for individual lobe for comparison to the relative SPECT lobar ventilation and perfusion. The absolute HPX-MRI percentage ventilation in each lobe was compared to the absolute CT percentage emphysema score calculated using a signal threshold method. Pearson's correlation and linear regression tests were performed to compare each imaging modality. RESULTS:Strong correlations were found between the relative lobar percentage ventilation with HPX-MRI and percentage ventilation SPECT (r?=?0.644; p?<?0.001) and percentage perfusion SPECT (r?=?0.767; p?<?0.001). The absolute CT percentage emphysema and HPX percentage ventilation correlation was also statistically significant (r?=?0.695, p?<?0.001). The whole lung HPX percentage ventilation correlated with the PFT measurements (FEV1 with r?=?-?0.886, p?<?0.001*, and FEV1/FVC with r?=?-?0.861, p?<?0.001*) better than the whole lung CT percentage emphysema score (FEV1 with r?=?-?0.635, p?=?0.027; and FEV1/FVC with r?=?-?0.652, p?=?0.021). CONCLUSION:Lobar ventilation with HPX-MRI showed a strong correlation with lobar ventilation and perfusion measurements derived from SPECT/CT, and is better than the emphysema score obtained with high-resolution CT. KEY POINTS:• The ventilation hyperpolarized xenon-129 MRI correlates well with ventilation and perfusion with SPECT/CT with the advantage of higher temporal and spatial resolution. • The hyperpolarized xenon-129 MRI correlates with the PFT measurements better than the high-resolution CT with the advantage of avoiding the use of ionizing radiation.

Project description:BACKGROUND:MRI of hyperpolarized 129 Xenon (HP 129 Xe) is increasingly utilized for investigating pulmonary function. The solubility of HP 129 Xe in lung tissue, blood plasma (Barrier), and red blood cells (RBC), with unique chemical shifts, enables spectroscopic imaging of potential imaging biomarkers of gas exchange and microstructural pulmonary physiology. PURPOSE:To quantify global average and regional repeatability of Barrier:gas, RBC:gas, and RBC:Barrier ratios derived from dissolved-phase 129 Xe imaging and their dependence on intervisit changes in lung inflation volume. STUDY TYPE:Prospective. POPULATION:Fourteen healthy volunteers. One subject was unable to complete the study resulting in 13 subjects for analysis (eight female, five male, ages 24-69, 53.8 ± 13.9). FIELD STRENGTH:1.5T. ASSESSMENT:Subjects were imaged using a 3D radial 1-point Dixon method to separate Barrier and RBC component signals, at two different timepoints, with ~1 month between visits. RBC:Gas, Barrier:Gas, and RBC:Barrier measures were compared across time and with pulmonary function tests (PFTs). STATISTICAL TESTS:Repeatablilty was quantified using Bland-Altman plots, coefficient of repeatability, coefficient of variation (CV), and intraclass correlation coefficients (ICCs). Dependence of imaging measures on PFTs and lung volume was evaluated using Spearman and Pearson correlation coefficients, respectively. Statistical significance was determined by F-test for intraclass correlations, and t-test for Spearman correlations and regression. RESULTS:Mean RBC:Gas, Barrier:Gas, and RBC:Barrier had CVs of 19.2%, 20.0%, and 11.5%, respectively, and had significant ICCs, equal to 0.78, 0.79, and 0.92, respectively. Intervisit differences in RBC:Barrier were significantly correlated with intervisit differences in DLCO (r = 0.93, P = 0.007). Significant correlations with intervisit lung volume differences and intervisit differences in mean RBC:Gas (r = -0.73, P = 0.005) and Barrier:Gas (r = -0.69, P = 0.009) were found. DATA CONCLUSION:Three commonly used 129 Xe MRI-based measures of gas-exchange show good repeatability, particularly the Barrier:RBC ratio, which did not depend on lung inflation volume and was strongly associated with intervisit changes in DLCO . LEVEL OF EVIDENCE:1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1182-1190.

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Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma.

Publications

Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma.

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