Three‐dimensional quantitative MRI of aerosolized gadolinium‐based nanoparticles and contrast agents in isolated ventilated porcine lungs

Abstract

PurposeThe objective of this study is to evaluate the suitability and performance of ultra‐short echo time (UTE) sequences for imaging and quantifying the deposition of nebulized MRI contrast agents in human‐sized lungs.MethodsNebulization of clinically used contrast agent or gadolinium‐based nanoparticles were performed using a commercial jet nebulizer in isolated and ventilated porcine lungs connected to a 3D‐printed human upper airways replica. MR images of isolated lungs were acquired on a 3T clinical MR scanner using 3D UTE sequences at different flip angles.Results3D acquisitions with isotropic millimetric resolution were obtained in less than 4 min. Images exhibit homogeneous and large MR signal enhancement (above 200%) following nebulization of both types of aerosols. Deposition of aerosol down to the level of the bronchi of secondary lobules was visualized. T1 values and the concentration of nanoparticles obtained by MRI were found to correlate with the amount of nebulized gadolinium3+ ions.ConclusionThe distribution of aerosolized gadolinium‐based contrast agent or nanoparticles can be visualized and quantified using UTE MRI in large animal ventilated lung model on a clinical MRI scanner. This protocol can be used for assessing and quantifying aerosol regional deposition with high spatial resolution (1 mm 3D isotropic) without ionizing radiation and could be applied in the future for diagnostic or therapeutic applications in patients.

Nano-delivery to the lung - by inhalation or other routes and why nano when micro is largely sufficient?

“…To reach this objective, innovative ex vivo respiratory models appear to be an interesting preclinical tool to assess aerosol regional deposition of nano-delivery systems in healthy and pathological-like respiratory tracts [165,201]. Composed of a 3D-printed Ear-Nose-Throat replica connected to ex vivo animal respiratory tract in a hypobaric chamber simulating passive ventilation, these models appear as an innovative and promising way to quantitatively assess aerosol deposition into the lungs and to transpose it more easily to human [202,203].…”

<p>Nebulised Gadolinium-Based Nanoparticles for a Multimodal Approach: Quantitative and Qualitative Lung Distribution Using Magnetic Resonance and Scintigraphy Imaging in Isolated Ventilated Porcine Lungs</p>

“…24,26 Composed a 3D-printed Ear-Nose-Throat (ENT) replica connected to a porcine respiratory tract (RT) in a sealed enclosure simulating passive ventilation, these models proved to be an innovative way to quantitatively assess aerosol deposition into the respiratory tract. 30,51 Hence, it could be easier to assess aerosol deposition into the lungs and then to transpose it to human.…”

“…The model was set in supine position with following breathing pattern: 15 cycles per minutes, tidal volume about 500 mL and dynamic compliance about 90 cmH 2 O/mL as previously described. 26,30 A scheme of the model and complete description are provided in Supplementary Information.…”

“…The protocol allowing the imaging of nebulised SRP in isolated porcine lungs was previously described. 30 Acquisitions were performed with a 3 Tesla whole body magnet (Vantage Galan 3T ZGO, Canon Medical Systems Corporation, Japan) using a T 1 -weighted 3D UTE (Ultra short Echo Time) MRI sequence. Detailed information about the imaging protocol are available in the Supplementary Information and in the paper from Crémillieux et al 30 Signal enhancement was defined as:…”

Multiparametric investigation of non functionalized-AGuIX nanoparticles in 3D human airway epithelium models demonstrates preferential targeting of tumor cells

“…An in vivo study of localized AGuIX ® intrathecal instillation in mice showed increased tumor targeting and radiotherapy efficiency compared to systemic injection [12,18,19]. As well, AGuIX ® aerosolization may represent a promising theranostic approach for the treatment of lung tumors and metastases [22]. In order to mimic NP's liquid aerosolization, we used two innovative 3D human models of the respiratory tract, one without tumor cells (MucilAir ™ /Epithelix) and one with A549 adenocarcinoma nodules (OncoCilAir ™ /Oncotheis) [23].…”