Aerosol deposition in the lungs of spontaneously breathing rats using Gd‐DOTA‐based contrast agents and ultra‐short echo time MRI at 1.5 Tesla

Wang, Hongchen; Sebrié, Catherine; Ruaud, Jean-Pierre; Guillot, Geneviève; Bouazizi, Khaoula; Willoquet, Georges; Maı̂tre, Xavier; Darrasse, Luc; Rochefort, Ludovic de

doi:10.1002/mrm.25617

Cited by 17 publications

(29 citation statements)

References 65 publications

(92 reference statements)

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“…A fraction of 7 mL of gadoterate meglumine (Gd‐DOTA) (Dotarem®; Guerbet, Villepinte, France) was aerosolized on line by a vibrating‐mesh nebulizer (Aeroneb® Solo; Aerogen, Galway, Ireland) and was administered to the free‐breathing rats during approximately 14 min. The aerodynamic size of the aerosols was measured by laser diffraction (Helos/BF; Sympatec, Germany) with an MMAD of 2.5 μm . The TV was estimated using a cine sequence synchronized with the animal's respiration, with the following parameters: TR/TE = 5.2/2.6 ms, T acq = 5.6 min, α = 60°, BW = 854 Hz, phases = 50, voxel = 1 mm and a gating adapted to respiratory cycles per minute.…”

Section: Methodsmentioning

confidence: 99%

“…Data were processed offline using MATLAB (Version 2012a; MathWorks, Natick, MA, USA). A semi‐automatic segmentation approach was used to regionally analyze the acquired data as described in our previous study . The segmentation relied on baseline signal intensity (SI) to distinguish voxels corresponding to the lung parenchyma (lower SI) from those corresponding to the vessels and the surrounding tissues (higher SI).…”

Section: Methodsmentioning

confidence: 99%

“…RSE at the end of nebulization was converted into a concentration map, with longitudinal molar relaxivity r 1 = 3.7/mM/s and baseline T 1,0 = 1.1 s for rat lung of both models at 1.5 T:

R_{1} = - \frac{1}{TR} ln ([], \frac{SI (C) / SI (0) (E_{1, 0} - 1) + E_{2, C} (1 - E_{1, 0} cos α)}{SI (C) / SI (0) (E_{1, 0} - 1) cos α + E_{2, C} (1 - E_{1, 0} cos α)}),

C = \frac{1}{r_{1}} ((), R_{1} - R_{1, 0})

with E 1, 0 = exp (−TR R 1, 0 ) and

E_{2, C} = exp ((), - normalT normalE C r_{2}^{*})

, where R 1,0 and R 1 are the pre‐ and post‐contrast longitudinal relaxation rates, respectively, and

r_{2}^{*}

is the transverse relaxivity. We have neglected the R 2 *‐related variation term E 2, C on the quantification of deposition because of the low concentration range and the short TE, and assumed that lung collapses in the asthmatic case do not affect T 1,0 …”

Section: Methodsmentioning

confidence: 99%

“…More recently nebulized Gd‐based nanoparticles, developed as multimodal imaging probes and radiosensitizing agents, were combined with UTE MRI to detect lung tumor nodules and improve radiotherapy . To favor translational developments, 3D UTE MRI was implemented at 1.5 T with spontaneous nose‐only inhalation of aerosolized Gd‐DOTA . The distributions of deposited aerosol were found homogeneous throughout the lungs and aerosol clearance followed similar trends in healthy subjects …”

Section: Introductionmentioning

confidence: 99%

“…To favor translational developments, 3D UTE MRI was implemented at 1.5 T with spontaneous nose‐only inhalation of aerosolized Gd‐DOTA . The distributions of deposited aerosol were found homogeneous throughout the lungs and aerosol clearance followed similar trends in healthy subjects …”

Section: Introductionmentioning

confidence: 99%

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Quantitative Gd‐DOTA‐based aerosol deposition mapping in the lungs of asthmatic rats using 3D UTE‐MRI

et al. 2018

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Asthma is a chronic respiratory disease, commonly treated with inhaled therapy. Better understanding of the mechanisms of aerosol deposition is required to improve inhaled drug delivery. Three‐dimensional ultrashort echo time (UTE) MRI acquisitions at 1.5 T were combined with spontaneous nose‐only inhalation of aerosolized gadolinium (Gd) to map the aerosol deposition and to characterize signal enhancement in asthmatic rat lungs. The rats were sensitized to ovalbumin (OVA) to develop asthmatic models and challenged before imaging by nebulization of OVA to trigger asthmatic symptoms. The negative controls were not sensitized or challenged by nebulization of saline. The animal lungs were imaged before and after administration of Gd‐based aerosol in freely breathing rats, by using a T1‐weighted 3D UTE sequence. A contrast‐enhanced quantitative analysis was performed to assess regional concentration. OVA‐sensitized rats had lower signal enhancement and lower deposited aerosol concentration. Their enhancement dynamics showed large inter‐subject variability. The signal intensity was homogeneously enhanced for controls while OVA‐sensitized rats showed heterogeneous enhancement. Contrast‐enhanced 3D UTE was applied with aerosolized Gd to efficiently measure spatially resolved deposition in asthmatic lungs. The small administered dose (around 1 μmol/kg body weight) and the use of standard clinical MRI suggest a potential application for the exploration of asthma.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…RSE at the end of nebulization was converted into a concentration map, with longitudinal molar relaxivity r 1 = 3.7/mM/s and baseline T 1,0 = 1.1 s for rat lung of both models at 1.5 T:

R_{1} = - \frac{1}{TR} ln ([], \frac{SI (C) / SI (0) (E_{1, 0} - 1) + E_{2, C} (1 - E_{1, 0} cos α)}{SI (C) / SI (0) (E_{1, 0} - 1) cos α + E_{2, C} (1 - E_{1, 0} cos α)}),

C = \frac{1}{r_{1}} ((), R_{1} - R_{1, 0})

with E 1, 0 = exp (−TR R 1, 0 ) and

E_{2, C} = exp ((), - normalT normalE C r_{2}^{*})

, where R 1,0 and R 1 are the pre‐ and post‐contrast longitudinal relaxation rates, respectively, and

r_{2}^{*}

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quantitative Gd‐DOTA‐based aerosol deposition mapping in the lungs of asthmatic rats using 3D UTE‐MRI

et al. 2018

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T₁, T₁ contrast, and Ernst‐angle images of four rat‐lung pathologies

Kuethe

Hix

Fredenburgh

2018

Magnetic Resonance in Med

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Purpose To initiate the archive of relaxation‐weighted images that may help discriminate between pulmonary pathologies relevant to acute respiratory distress syndrome. MRI has the ability to distinguish pathologies by providing a variety of different contrast mechanisms. Lungs have historically been difficult to image with MRI but image quality is sufficient to begin cataloging the appearance of pathologies in T1‐ and T2‐weighted images. This study documents T1 and the use of T1 contrast with four experimental rat lung pathologies. Methods Inversion‐recovery and spoiled steady state images were made at 1.89 T to measure T1 and document contrast in rats with atelectasis, lipopolysaccharide‐induced inflammation, ventilator‐induced lung injury (VILI), and injury from saline lavage. Higher‐resolution Ernst‐angle images were made to see patterns of lung infiltrations. Results T1‐weighted images showed minimal contrast between pathologies, similar to T1‐weighted images of other soft tissues. Images taken shortly after magnetization inversion and displayed with inverted contrast highlight lung pathologies. Ernst‐angle images distinguish the effects of T1 relaxation and spin density and display distinctive patterns. T1 for pathologies were: atelectasis, 1.25 ± 0.046 s; inflammation from instillation of lipopolysaccharide, 1.24 ± 0.015 s; VILI, 1.55 ± 0.064 s (p = 0.0022 vs. normal lung); and injury from saline lavage, 1.90±0.080 s (p = 0.0022 vs. normal lung; p = 0.0079 vs. VILI). T1 of normal lung and erector spinae muscle were 1.25 ± 0.028 s and 1.02 ± 0.027 s, respectively (p = 0.0022). Conclusions Traditional T1‐weighting is subtle. However, images made with inverted magnetization and inverted contrast highlight the pathologies and Ernst‐angle images aid in distinguishing pathologies.

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Proton MRI Based Ventilation Imaging: Oxygen-Enhanced Lung MRI and Alternative Approaches

Dietrich

2016

MRI of the Lung

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Aerosol deposition in the lungs of spontaneously breathing rats using Gd‐DOTA‐based contrast agents and ultra‐short echo time MRI at 1.5 Tesla

Abstract: The UTE protocol with nebulized Gd-DOTA is replicable to significantly enhance the lung parenchyma and to map aerosol deposition. This functional strategy, applied in a clinical system with a clinical nebulization setup and a low inhaled dose, suggests a feasible translation to human.

Cited by 17 publications

References 65 publications

Quantitative Gd‐DOTA‐based aerosol deposition mapping in the lungs of asthmatic rats using 3D UTE‐MRI

Quantitative Gd‐DOTA‐based aerosol deposition mapping in the lungs of asthmatic rats using 3D UTE‐MRI

T₁, T₁ contrast, and Ernst‐angle images of four rat‐lung pathologies

Proton MRI Based Ventilation Imaging: Oxygen-Enhanced Lung MRI and Alternative Approaches

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Aerosol deposition in the lungs of spontaneously breathing rats using Gd‐DOTA‐based contrast agents and ultra‐short echo time MRI at 1.5 Tesla

Abstract: The UTE protocol with nebulized Gd-DOTA is replicable to significantly enhance the lung parenchyma and to map aerosol deposition. This functional strategy, applied in a clinical system with a clinical nebulization setup and a low inhaled dose, suggests a feasible translation to human.

Cited by 17 publications

References 65 publications

Quantitative Gd‐DOTA‐based aerosol deposition mapping in the lungs of asthmatic rats using 3D UTE‐MRI

Quantitative Gd‐DOTA‐based aerosol deposition mapping in the lungs of asthmatic rats using 3D UTE‐MRI

T1, T1 contrast, and Ernst‐angle images of four rat‐lung pathologies

Proton MRI Based Ventilation Imaging: Oxygen-Enhanced Lung MRI and Alternative Approaches

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Product

Resources

About

T₁, T₁ contrast, and Ernst‐angle images of four rat‐lung pathologies