High resolution propagation-based imaging system for in vivo dynamic computed tomography of lungs in small animals

Abstract

We have developed an x-ray imaging system for in vivo four-dimensional computed tomography (4DCT) of small animals for pre-clinical lung investigations. Our customized laboratory facility is capable of high resolution in vivo imaging at high frame rates. Characterization using phantoms demonstrate a spatial resolution of slightly below 50 μm at imaging rates of 30 Hz, and the ability to quantify material density differences of at least 3%. We benchmark our system against existing small animal pre-clinical CT scanners using a quality factor that combines spatial resolution, image noise, dose and scan time. In vivo 4DCT images obtained on our system demonstrate resolution of important features such as blood vessels and small airways, of which the smallest discernible were measured as 55-60 μm in cross section. Quantitative analysis of the images demonstrate regional differences in ventilation between injured and healthy lungs.

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

“…Note that these distances depend on pixel size and X-ray energy, which we have also stated in Table 1. We have found that rat/mouse/rabbit pup lung imaging is best with a propagation distance of around 2 m at a synchrotron (Kitchen et al, 2004), slightly less at a compact synchrotron where penumbral blurring is a consid-eration (Gradl et al, 2018), and slightly more at a micro-focus source where penumbral blurring is small and magnification reduces the relative phase effects at a given distance (Preissner et al, 2018). For high-resolution imaging of the airway surface, where a small pixel size captures narrow bright/dark bands, distances can be as short as 10 cm for a rat trachea and 30 cm for a mouse trachea (where the projected tissue thickness of the smaller airway will contain weaker gradients).…”

Visualizing treatment delivery and deposition in mouse lungs using in vivo x-ray imaging

“…A C C E P T E D M A N U S C R I P T 43,44], mean that the widespread use of dynamic propagation-based imaging is moving closer to a reality. For example, Larsson et al used a liquid-metal-jet x-ray source to capture phase-contrast tomographic images of an excised air-filled mouse lung [45], Preissner et al captured in vivo mouse lung structure [46], and Kim et al performed 4DCT measurements at a liquid-metal-jet source to explore the effect of mechanical ventilation on the lung [47]. Using an inverse Compton source, we have recently shown in vivo PCXI of mouse respiratory function [48].…”

Application of a novel in vivo imaging approach to measure pulmonary vascular responses in mice

“…; Preissner et al. ). These recent advances in preclinical imaging provide further steps toward development in the area of clinical applications (Bravin et al.…”