Abstract
To understand the determinants of inhaled aerosol particle distribution and targeting in the lung, knowledge of regional deposition, lung morphology and regional ventilation, is crucial. No single imaging modality allows the acquisition of all such data together. Here we assessed the feasibility of dual-energy synchrotron radiation imaging to this end in anesthetized rabbits; both in normal lung (n = 6) and following methacholine (MCH)-induced bronchoconstriction (n = 6), a model of asthma. We used K-edge subtraction CT (KES) imaging to quantitatively map the regional deposition of iodine-containing aerosol particles. Morphological and regional ventilation images were obtained, followed by quantitative regional iodine deposition maps, after 5 and 10 minutes of aerosol administration. Iodine deposition was markedly inhomogeneous both in normal lung and after induced bronchoconstrition. Deposition was significantly reduced in the MCH group at both time points, with a strong dependency on inspiratory flow in both conditions (R2 = 0.71; p < 0.0001). We demonstrate for the first time, the feasibility of KES CT for quantitative imaging of lung deposition of aerosol particles, regional ventilation and morphology. Since these are among the main factors determining lung aerosol deposition, we expect this imaging approach to bring new contributions to the understanding of lung aerosol delivery, targeting, and ultimately biological efficacy.
Highlights
To understand the determinants of inhaled aerosol particle distribution and targeting in the lung, knowledge of regional deposition, lung morphology and regional ventilation, is crucial
We demonstrate for the first time, the feasibility of K-edge subtraction computed x-ray tomography (CT) (KES) CT for quantitative imaging of lung deposition of aerosol particles, regional ventilation and morphology
Aerosol particle deposition in the lower respiratory tract depends on a number of factors, including mass median aerodynamic diameter (MMAD), the inspiratory flow velocity and the flow regime, and the lung airway morphology[4]
Summary
To understand the determinants of inhaled aerosol particle distribution and targeting in the lung, knowledge of regional deposition, lung morphology and regional ventilation, is crucial. We demonstrate for the first time, the feasibility of KES CT for quantitative imaging of lung deposition of aerosol particles, regional ventilation and morphology. Different strategies are being developed in order to target aerosol particles to specific regions of the lung, preferentially those that are more affected by a disease process The success of such strategies in translating into clinical applications critically depends on imaging techniques allowing for both the quantitative determination of aerosol deposition, and the morphology of the bronchial tree, ideally using a single imaging modality with a high spatial resolution in order to be applicable in preclinical small animal models. Because these techniques do not allow imaging lung morphology, they are combined with computed x-ray tomography (CT), which requires co-registration of the acquired images on the combined instruments
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