Aerosol Delivery in Ventilated Newborn Pigs: An MRI Evaluation

Abstract

Pulmonary deposition of inhaled drugs in ventilated neonates has not been studied in vivo. The objective of this study was to evaluate pulmonary delivery of gadopentetate dimeglumine (Gd-DTPA) following nebulization in ventilated piglets using magnetic resonance imaging. Seven ventilated piglets (5 Ϯ 2 d old, weight 1.8 Ϯ 0.5 kg) were scanned in the Bruker/Siemens 4T magnetic resonance scanner using T1 weighted spin-echo sequence. Aerosols of Gd-DTPA were generated continuously using the MiniHeart jet nebulizer. Breath-hold coronal images were obtained before and every 10 min during aerosolized Gd-DTPA for 90 min. Signal intensity (SI) changes over the lungs, kidneys, liver, skeletal muscle, and heart were evaluated. A significant increase in SI was observed in the lungs, kidney, and liver at 10, 20, and 40 min respectively after start of aerosol. At the end of 90 min, the SI increased by 95%, 101%, and 426% over the right lung, left lung, and kidney, respectively. A much smaller increase in SI was observed over the liver. In conclusion, we have demonstrated effective pulmonary aerosol delivery within 10 min of contrast nebulization in ventilated piglets. Contrast visualization in the kidneys within 20 min of aerosol initiation reflects alveolar absorption, glomerular filtration and renal concentration. (Pediatr Res 64: 159-164, 2008)

Regional Distribution of Aerosol Deposition in Rat Lungs Using Magnetic Resonance Imaging

“…These include gamma scintigraphy, 3,5,24,28 PET, 7 SPECT, 8,11 and more recently MRI. 13,19 Gamma cameras capture either 2D (gamma scintigraphy) or 3D (SPECT) images of deposited particles labeled with a radionuclide (typically 99 m T c ) to measure peripheral and central distribution of deposition 5 as well as lung clearance. 3 The advantages of 3D PET lie in the ability to achieve a better image quality than SPECT, 7 as well as the capability to attach the radionuclide label directly to the drug molecule.…”

“…Thus far, deposition quantification using MRI has only been performed in animal studies, using either iron oxide particles 13 or gadolinium. 4,9,14,19,21 …”

“…This work also improved on several previous MRI studies in animals that only reported global measures of ventilation 4,9,14 or whole lung deposition. 19,21 …”

Airway Deposition of Nebulized Gene Delivery Nanocomplexes Monitored by Radioimaging Agents

“…The distribution of radioactivity was compared with the localization of the transgene, as determined by real-time PCR, in tissue samples taken from different regions of the lung, to assess whether the radiocompound and the delivered gene were colocalized, and thus to assess the potential of this approach for noninvasively monitoring vector deposition in patients. Although mechanical simulators are available (26), and despite variations in the aerosol deposition because of the structure of the respiratory tract (27,28), porcine models are used extensively for pediatric respiratory research and beyond (29)(30)(31). The porcine respiratory system was selected for these experiments because it resembles that of humans in terms of anatomy, physiology, biochemistry, and size (32,33).…”

At the Frontiers of Understanding: Inhaled Aerosols in Neonates: Commentary on articles by Minocchieri et al. on page 141, and Sood et al. on page 159

“…Such studies have not been done in the past due to radiologic exposure issues with conventional radioisotope methods of assessing deposition. The article by Sood et al (10), in the present issue, aims at circumventing these radiologic exposure concerns. By showing that magnetic resonance imaging (MRI) can be used to assess regional deposition in newborn pigs using a paramagnetic contrast agent (Gadopentetate dimeglumine: Gd-DTPA) added to a nebulized solution, Sood et al set the stage for in vivo studies aimed at improving our poor knowledge of in vivo aerosol deposition in infants and children.…”