Dataset Information

Longitudinal free-breathing MRI measurement of murine lung physiology in a progressive model of lung fibrosis.

ABSTRACT: To longitudinally monitor progressive fibrosis in the transforming growth factor-? (TGF-?) transgenic mouse model of lung fibrosis, we used retrospective self-gating ultrashort echo time (UTE) magnetic resonance imaging (MRI) to image mouse lung at baseline and after 4 and 8 wk of fibrosis initiation via doxycycline administration. Only bitransgenic mice were used in this study and divided into two cohorts: six mice were fed doxycycline food to induce lung fibrosis (referred to as Dox cohort), and five other mice were fed normal food (referred to as control cohort). Lung mechanics, histology, and hydroxyproline were assessed after the final MRI. A linear mixed-effects model was used to analyze MRI-derived longitudinal lung-function parameters. Tidal volume decreased at a rate of -0.016?±?0.002 ml/week [?2(1)?=?16.48, P < 0.001] for Dox cohort and increased at a rate of 0.010?±?0.003 ml/week [?2(1)?=?6.37, P = 0.01] for control cohort. Minute ventilation decreased at a rate of -1.71?±?0.26 ml·min-1·wk-1 [?2(1)?=?14.04, P < 0.001] for Dox cohort but did not change significantly over time for control cohort. High-density lung volume percentage increased at a rate of 3.9 ± 0.7%/wk for Dox cohort [?2(1)?=?11.47, P < 0.001] but did not change significantly over time for control cohort. MRI-derived lung structure and function parameters were strongly correlated with pleural thickness, hydroxyproline content, lung compliance, airway resistance, and airway elastance. We conclude that self-gating UTE MRI could be used to longitudinally monitor lung fibrosis in the TGF-? transgenic mouse model. NEW & NOTEWORTHY Self-gating UTE MRI was used to monitor morphology and physiology in lung fibrosis in a transforming growth factor-? transgenic mouse model. Tidal volume was shown for the first time to correlate strongly with conventional metrics of fibrosis such as hydroxyproline and pleural thickness.

SUBMITTER: Guo J

PROVIDER: S-EPMC6485694 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Longitudinal free-breathing MRI measurement of murine lung physiology in a progressive model of lung fibrosis.

Guo Jinbang J Hardie William D WD Cleveland Zackary I ZI Davidson Cynthia C Xu Xuefeng X Madala Satish K SK Woods Jason C JC

Journal of applied physiology (Bethesda, Md. : 1985) 20190207 4

To longitudinally monitor progressive fibrosis in the transforming growth factor-α (TGF-α) transgenic mouse model of lung fibrosis, we used retrospective self-gating ultrashort echo time (UTE) magnetic resonance imaging (MRI) to image mouse lung at baseline and after 4 and 8 wk of fibrosis initiation via doxycycline administration. Only bitransgenic mice were used in this study and divided into two cohorts: six mice were fed doxycycline food to induce lung fibrosis (referred to as Dox cohort), a ...[more]

PMID: 30730810

Similar Datasets

Project description:To characterize and quantify free breathing lung tissue motion distributions.Forty seven patient data sets were acquired using a 4DCT protocol consisting of 25 ciné scans at abutting couch positions on a 16-slice scanner. The tidal volume of each scan was measured by simultaneously acquiring spirometry and an abdominal pneumatic bellows. The concept of a characteristic breath was developed to manage otherwise natural breathing pattern variations. The characteristic breath was found by first dividing the breathing traces into individual breaths, from maximum exhalation to maximum exhalation. A linear breathing drift model was assumed and the drift removed for each breath. Breaths that exceeded one standard deviation in period or amplitude were removed from further analysis. A characteristic breath was defined by normalizing each breath to a common amplitude, aligning the peak inhalation times for all of the breaths, and determining the average time at each tidal volume, keeping inhalation and exhalation separate. Breathing motion trajectories were computed using a previously published five-dimensional lung tissue trajectory model which expresses the position of internal lung tissue, X, as: X(v,f:X0)=X0+α(X0)v+β(X0)f, where X0 is the internal lung tissue position at zero tidal volume and zero airflow, the scalar values v and f are the measured tidal volume and airflow, respectively, and the vectors α and β are fitted free parameters. In order to characterize the motion patterns, the trajectory elongations were examined throughout the subject's lungs. Elongation was defined here by generating a rectangular bounding box with one side parallel to the α vector and the box oriented in the plane defined by the α and β motion vectors. Hysteresis motion was defined as the ratio of the box dimensions aligned orthogonal to and parallel to the α vector. The 15th and 85th percentile of the elongation were used to characterize tissue trajectory hysteresis.The 15th and 85th percentile bounding box elongations were 0.090 ± 0.005 and 0.083 ± 0.013 in the upper left lung and 0.187 ± 0.037 and 0.203 ± 0.053, in the lower left lung. The 15th and 85th percentiles for the upper right lung were 0.092 ± 0.006 and 0.085 ± 0.013, and 0.184 ± 0.038, and 0.196 ± 0.043 in the lower right lung. Both percentiles were calculated for tidal volume displacements between 5 and 15 mm. In the left lung, the average elongations in the upper and lower lung were ζ=0.120 ± 0.064 and ζ=0.090 ± 0.055, respectively. The average elongations in the upper and lower right lung were ζ=0.107 ± 0.060 and ζ=0.082 ± 0.048, respectively. The elongation varied smoothly throughout the lungs.The hysteresis motion was relatively small compared to the volume-filling motion, contributing between 8% and 20% of the overall motion. Statistically significant differences were observed in the range of hysteresis contribution for upper and lower lung regions. The characteristic breath process provided an excellent method for defining an average breath. The characteristic breath had continuous tidal volume and airflow characteristics when the breath was continuously repeated,useful for generating patterns representative of realistic motion for breathing motion studies.

Project description:ObjectivesThe purpose of this study was to evaluate the ability of a novel cardiac magnetic resonance (CMR) real-time phase contrast (RT-PC) flow measurement technique to reveal the discordant respirophasic changes in mitral and tricuspid valve in flow indicative of the abnormal hemodynamics seen in constrictive pericarditis (CP).BackgroundDefinitive diagnosis of CP requires identification of constrictive hemodynamics with or without pericardial thickening. CMR to date has primarily provided morphological assessment of the pericardium.MethodsSixteen patients (age 57 ± 13 years) undergoing CMR to assess known or suspected CP and 10 controls underwent RT-PC that acquired simultaneous mitral valve and tricuspid valve inflow velocities over 10 s of unrestricted breathing. The diagnosis of CP was confirmed via clinical history, diagnostic imaging, cardiac catheterization, intraoperative findings, and histopathology.ResultsTen patients had CP, all with increased pericardial thickness (6.2 ± 1.0 mm). RT-PC imaging demonstrated discordant respirophasic changes in atrioventricular valve inflow velocities in all CP patients, with mean ± SD mitral valve and tricuspid valve inflow velocity variation of 46 ± 20% and 60 ± 15%, respectively, compared with 16 ± 8% and 24 ± 11% in patients without CP (p < 0.004 vs. patients with CP for both) and 17 ± 5% and 31 ± 13% in controls (p < 0.001 vs. patients with CP for both). There was no difference in atrioventricular valve inflow velocity variation between patients without CP compared with controls (p > 0.3 for both). Respiratory variation exceeding 25% across the mitral valve yielded a sensitivity of 100%, a specificity of 100%, and an area under the receiver-operating characteristic curve of 1.0 to detect CP physiology. Using a cutoff of 45%, variation of transtricuspid valve velocity had a sensitivity of 90%, a specificity of 88%, and an area under the receiver-operating characteristic curve of 0.98.ConclusionsAccentuated and discordant respirophasic changes in mitral valve and tricuspid valve inflow velocities characteristic of CP can be identified noninvasively with RT-PC CMR. When incorporated into existing CMR protocols for imaging pericardial morphology, RT-PC CMR provides important hemodynamic evidence with which to make a definite diagnosis of CP.

Dataset Information

Longitudinal free-breathing MRI measurement of murine lung physiology in a progressive model of lung fibrosis.

Publications

Longitudinal free-breathing MRI measurement of murine lung physiology in a progressive model of lung fibrosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure