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

Abstract

The toxic or therapeutic effect of an inhaled aerosol is highly dependent upon the site and extent of deposition in the lung. A novel MRI-based method was used to quantify the spatial distribution of particles in the rat lung. Rats were exposed to 0.95 μm-diameter iron oxide particles in a controlled manner (N=6) or to particle-free air (N=6). Lungs were fixed in 3 % glutaraldehyde by vascular perfusion, excised and imaged in a 3T scanner using a gradient-echo imaging protocol. The signal decay rate, R2∗, was measured in each voxel of the entire left lung (1 mm thick slices). R2∗ was significantly higher in exposed animals (0.0065 ± 0.0006 msec−1) than in controls (0.0050 ± 0.0003 msec−1, p<0.001). A calibration curve between R2∗ and concentration of deposited particles (Cpart) was obtained by imaging gel samples with known particle concentrations. Regional deposition was assessed by comparing Cpart between the outer (Cpart,peripheral) and inner (Cpart,central) areas on each transaxial slice, and expressed as the cp ratio. Cpart,peripheral (1.54 ± 0.70 μgml) was significantly, higher than Cpart,central ml (1.00 ± 0.39 μgml, p<0.05), resulting in a cp ratio of 0.65. This method may be used in future studies to quantify spatial distribution of deposited particles in healthy and diseased lungs.

Airflow and Particle Deposition Simulations in Health and Emphysema: From In Vivo to In Silico Animal Experiments

“…38,39 The global respiratory values, i.e. resistance and compliance, were estimated from the airway pressure and the breathing parameters measured during the experiments.…”

“…38,39 Five healthy and five elastase induced emphysematous 39 anesthetized rats (body weight of 409 ± 26 grams and 432 ± 46 grams, respectively) were mechanically ventilated. During inhalation, the piston pump pushed 2.2 mL of particle-laden air into the lung at a breathing frequency (BF) of 80 $1\frac{breaths}{min}$.…”

“…The particles had a 0.95 μm geometric diameter and a density of 1.35 $1\frac{g}{c{m}^3}$. 38 At the end of inhalation, the rat passively exhaled through a tube into a jar filled with water, subjecting the rat to a constant 1 cmH 2 O end expiratory pressure ( P Peep ).…”

“…The goal of the current work was to develop a multi-scale respiratory model to simulate airflow and particle deposition to replicate animal aerosol exposure experiments 38 in both healthy and emphysematous rats. 39 In the experimental study, pressure was measured over time at the trachea and the maximum pressure was significantly lower (p = 0.01) in the emphysematous rats compared to the healthy rats.…”

Nanomaterial translocation–the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs–a review

“…In all reality, any potential pathogenic effects of inhaled NMs in the pulmonary system are dependent on a substantial lung burden which is determined by the site and extent of deposition in the lung and eventual clearance (Oakes et al 2013, Pauluhn, 2014. This deposition and clearance takes place throughout the respiratory tract and is heavily influenced by material size and surface properties (Muhlfeld et al 2008).…”