Respiratory-gated KES imaging of a rat model of acute lung injury at the Canadian Light Source

Abstract

In this study, contrast-enhanced X-ray tomographic imaging for monitoring and quantifying respiratory disease in preclinical rodent models is proposed. A K-edge imaging method has been developed at the Canadian Light Source to very accurately obtain measurements of the concentration of iodinated contrast agent in the pulmonary vasculature and inhaled xenon in the airspaces of rats. To compare the iodine and xenon concentration maps, a scout projection image was acquired to define the region of interest within the thorax for imaging and to ensure the same locations were imaged in each K-edge subtraction (KES) acquisition. A method for triggering image acquisition based on the real-time measurements of respiration was also developed to obtain images during end expiration when the lungs are stationary, in contrast to other previously published studies that alter the respiration to accommodate the image acquisition. In this study, images were obtained in mechanically ventilated animals using physiological parameters at the iodine K-edge in vivo and at the xenon K-edge post mortem (but still under mechanical ventilation). The imaging techniques were performed in healthy Brown Norway rats and in age-matched littermates that had an induced lung injury to demonstrate feasibility of the imaging procedures and the ability to correlate the lung injury and the quantitative measurements of contrast agent concentrations between the two KES images. The respiratory-gated KES imaging protocol can be easily adapted to image during any respiratory phase and is feasible for imaging disease models with compromised lung function.

Keywords: K-edge subtraction; contrast enhanced; in vivo imaging; lung injury; respiratory gated.

Figure 1

Custom-designed stereotaxic holder to position the rats vertically for the imaging sessions. The hole at the bottom allows access to the tail for the contrast agent injection via the tail vein catheter and manages the connectors for physiological monitoring. The holder is positioned on the rotation stage for acquisition of the projections for the CT reconstruction.

Figure 2

Synchrotron imaging data. (a) A projection image used to select the range for axial slices. (b) Tomographic reconstruction through the middle of the lungs and heart obtained during end expiration. (c) KES image of the iodine within the vasculature of the rat. (d) Corresponding KES image of the xenon in the airspaces of the lungs.

Figure 3

Representative H&E slides for (a) a control rat and (b) a rat instilled with LPS. Areas of inflammation are outlined within the lung tissue. The % inflammation for each slide is calculated as the total area of inflamed regions divided by the entire tissue area.