scholarly journals MRI-based measurements of aerosol deposition in the lung of healthy and elastase-treated rats

2014 ◽  
Vol 116 (12) ◽  
pp. 1561-1568 ◽  
Author(s):  
Jessica M. Oakes ◽  
Ellen C. Breen ◽  
Miriam Scadeng ◽  
Ghislain S. Tchantchou ◽  
Chantal Darquenne

Aerosolized drugs are increasingly being used to treat chronic lung diseases or to deliver therapeutics systemically through the lung. The influence of disease, such as emphysema, on particle deposition is not fully understood. With the use of magnetic resonance imaging (MRI), the deposition pattern of iron oxide particles with a mass median aerodynamic diameter of 1.2 μm was assessed in the lungs of healthy and elastase-treated rats. Tracheostomized rats were ventilated with particles, at a tidal volume of 2.2 ml, and a breathing frequency of 80 breaths/min. Maximum airway pressure was significantly lower in the elastase-treated (Paw = 7.71 ± 1.68 cmH2O) than in the healthy rats (Paw = 10.43 ± 1.02 cmH2O; P < 0.01). This is consistent with an increase in compliance characteristic of an emphysema-like lung structure. Following exposure, lungs were perfusion fixed and imaged in a 3T MR scanner. Particle concentration in the different lobes was determined based on a relationship with the MR signal decay rate, R2*. Whole lung particle deposition was significantly higher in the elastase-treated rats (CE,part = 3.03 ± 0.61 μm/ml) compared with the healthy rats (CH,part = 1.84 ± 0.35 μm/ml; P < 0.01). However, when particle deposition in each lobe was normalized by total deposition in the lung, there was no difference between the experimental groups. However, the relative dispersion [RD = standard deviation/mean] of R2* was significantly higher in the elastase-treated rats (RDE = 0.32 ± 0.02) compared with the healthy rats (RDH = 0.25 ± 0.02; P < 0.01). These data show that particle deposition is higher and more heterogeneously distributed in emphysematous lungs compared with healthy lungs.

2009 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
Eyk Schellenberger

Superparamagnetic iron oxide nanoparticles have been established as sensitive probes for magnetic resonance imaging (MRI). While the majority of specific nanosensors are based on sterically stabilized iron oxide particles, the focus of this review is on the use of very small iron oxide particles (VSOPs) that are electrostatically stabilized by an anionic citrate acid shell. We used VSOPs to develop target-specific as well as protease-activatable nanosensors for molecular MRI.


2005 ◽  
Vol 4 (2) ◽  
pp. 153535002005041 ◽  
Author(s):  
Uwe Himmelreich ◽  
Ralph Weber ◽  
Pedro Ramos-Cabrer ◽  
Susanne Wegener ◽  
Korinna Kandal ◽  
...  

In vivo monitoring of cells labeled with paramagnetic iron oxide particles by magnetic resonance imaging (MRI) is complicated by intrinsic contrast of blood vessels. Distinction between T2* effects caused by blood vessels from those caused by labeled cells was so far only possible after carefully following the location of hypointense regions through subsequent slices of T2*-weighted 3-D MRI datasets, a procedure that is time consuming and not always reliable in the case of smaller blood vessels. Here, we demonstrate that the modification of the inhalation gas mixture from the routinely used composition 35% O2 and 65% N2O to a mixture containing 95% O2 and 5% CO2 results in a contrast suppression of most small blood vessels and reduces the intrinsic T2* effect of large vessels dramatically in an animal model. This change in protocol of physiological conditions was well tolerated by all studied animals, even over prolonged experimental times. The changed inhalation gas mixture thus provides a more reliable identification method for small clusters of iron oxide labeled cells in vivo.


2021 ◽  
Vol 23 (3) ◽  
pp. 1248-1258
Author(s):  
Shannon M. North ◽  
Steven P. Armes

An atom-efficient, wholly aqueous one-pot synthesis of zwitterionic diblock copolymers has been devised. Such copolymers can serve as highly effective aqueous dispersants for nano-sized transparent yellow iron oxide particles.


2021 ◽  
Vol 11 (5) ◽  
pp. 431
Author(s):  
Sabine Hofer ◽  
Norbert Hofstätter ◽  
Albert Duschl ◽  
Martin Himly

COVID-19, predominantly a mild disease, is associated with more severe clinical manifestation upon pulmonary involvement. Virion-laden aerosols and droplets target different anatomical sites for deposition. Compared to droplets, aerosols more readily advance into the peripheral lung. We performed in silico modeling to confirm the secondary pulmonary lobules as the primary site of disease initiation. By taking different anatomical aerosol origins into consideration and reflecting aerosols from exhalation maneuvers breathing and vocalization, the physicochemical properties of generated respiratory aerosol particles were defined upon conversion to droplet nuclei by evaporation at ambient air. To provide detailed, spatially-resolved information on particle deposition in the thoracic region of the lung, a top-down refinement approach was employed. Our study presents evidence for hot spots of aerosol deposition in lung generations beyond the terminal bronchiole, with a maximum in the secondary pulmonary lobules and a high preference to the lower lobes of both lungs. In vivo, initial chest CT anomalies, the ground glass opacities, resulting from partial alveolar filling and interstitial thickening in the secondary pulmonary lobules, are likewise localized in these lung generations, with the highest frequency in both lower lobes and in the early stage of disease. Hence, our results suggest a disease initiation right there upon inhalation of virion-laden respiratory aerosols, linking the aerosol transmission route to pathogenesis associated with higher disease burden and identifying aerosol transmission as a new independent risk factor for developing a pulmonary phase with a severe outcome.


2014 ◽  
Vol 59 (5) ◽  
pp. 1472
Author(s):  
J.M.S. Chan ◽  
C. Monaco ◽  
M. Wylezinska-Arridge ◽  
J.L. Tremoleda ◽  
R.G.J. Gibbs

2009 ◽  
Vol 4 (1) ◽  
pp. 24-32 ◽  
Author(s):  
Geralda A. F. van Tilborg ◽  
Tessa Geelen ◽  
Hans Duimel ◽  
Paul H. H. Bomans ◽  
Peter M. Frederik ◽  
...  

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