Variability of In Vivo Fluid Dose Distribution in Mouse Airways Is Visualized by High-Speed Synchrotron X-Ray Imaging

Abstract

With adequate imaging rate and fluid dose parameters, this study shows the utility of synchrotron PCXI for determining the post-delivery behavior and fate of fluid doses such as those used in in vivo gene transfer or pharmaceutical studies.

Multimodal Precision Imaging of Pulmonary Nanoparticle Delivery in Mice: Dynamics of Application, Spatial Distribution, and Dosimetry

“…As mentioned above, most of the standard imaging modalities (e.g., PA, US, CT, SPECT, PET, and MRI) are unable to visualize pulmonary fluid delivery dynamics at 1 Hz under in vivo conditions in mice mainly due to the poor spatial and temporal resolution . Recently, some multimodal imaging techniques have been used for determination of NP biodistribution and bioactivity in preclinical research.…”

“…Also, quantitative imaging of co‐localization of tumor associated macrophages with therapeutic 64 Cu‐labeled polyglucose nanoparticle in an orthotopic model of lung adenocarcinoma was accomplished via PET, in vivo confocal microscopy, and tissue‐cleared LSFM . PCXI has already been applied for ex vivo and in vivo studies on mucociliary transport of large microparticles or 5–100 µm fibers in the trachea or upper airways of animal models such as mice and pigs and for monitoring the delivery of liquids to murine lungs via nose or intubated cannula delivery . Moreover, several common bulk particulates (e.g., lead dust, quarry dust, glass beads, asbestos, and Galena with size ≥ 5 µm) were tracked in live animal trachea airways by PCXI, showing the high variability in particle movement during mucociliary transport .…”

“…Consequently, the penetration depth of light, sensitivity, and quantification ability offered by PA imaging are not sufficient for determination of NM biodistribution and pharmacodynamics in the lungs. X‐ray‐based approaches (PCXI and CT) have been recently applied to monitor the pulmonary fluid delivery dynamics and deposition and lung pathophysiological state with high temporal and spatial resolution. The major challenges posed by X‐ray modalities are that they are incapable of assessing NM bioactivity and for visualizing NM at cellular resolution.…”

Methods for dynamic synchrotron X-ray respiratory imaging in live animals

“…The second category of studies are those aiming to test the effects of medical treatment or intervention. This has included visualizing the delivery of treatments (Donnelley et al, 2013;Porra et al, 2018;Gradl et al, 2019a) and the effect of treatments on a micrometre-scale [e.g. on mucociliary clearance or airway surface liquid depth (Morgan et al, 2014;Luan et al, 2017)] and the effect of interventions at a whole-organ scale [e.g.…”

Imaging regional lung function: A critical tool for developing inhaled antimicrobial therapies

“…PBI has been used to measure airway surface liquid depth, specifically for assessment of therapies for cystic fibrosis lung disease [95,96]. Donnelley et al [97] measured the variability of in vivo fluid dose distribution in liquid doses delivered through the pulmonary system. The affect of airway hydrating therapies on mucociliary transport [98,99] has also recently been investigated using synchrotron phase contrast imaging.…”