Anatomical and functional imaging of myocardial infarction in mice using micro‐CT and eXIA 160 contrast agent

Abstract

Non-invasive small animal imaging techniques are essential for evaluation of cardiac disease and potential therapeutics. A novel preclinical iodinated contrast agent called eXIA 160 has recently been developed, which has been evaluated for micro-CT cardiac imaging. eXIA 160 creates strong contrast between blood and tissue immediately after its injection and is subsequently taken up by the myocardium and other metabolically active tissues over time. We focus on these properties of eXIA and show its use in imaging myocardial infarction in mice. Five C57BL/6 mice were imaged ~ 2 weeks after LAD coronary artery ligation. Six C57BL/6 mice were used as controls. Immediately after injection of eXIA 160, an enhancement difference between blood and myocardium of ~340 HU enabled cardiac function estimation via 4D micro-CT scanning with retrospective gating. Four hours post-injection, the healthy perfused myocardium had a contrast difference of ~140 HU relative to blood while the infarcted myocardium showed no enhancement. These differences allowed quantification of infarct size via dual energy micro-CT. In vivo micro-SPECT imaging and ex vivo TTC staining provided validation for the micro-CT findings. Root mean squared error of infarct measurements was 2.7% between micro-CT and SPECT, and 4.7% between micro-CT and TTC. Thus, micro-CT with eXIA 160 can be used to provide both morphological and functional data for preclinical studies evaluating myocardial infarction and potential therapies. Further studies are warranted to study the potential use of eXIA 160 as a CT molecular imaging tool for other metabolically active tissues in the mouse.

<em>In Vivo</em> Quantitative Assessment of Myocardial Structure, Function, Perfusion and Viability Using Cardiac Micro-computed Tomography

“…Interestingly, the areas of hypoenhancement can be visually seen on short-axial cross-section images (Figure 1) and can be easily quantified as shown in Figure 3. This was not possible in the study by Befeda et al and could be explained by greater noise of the MicroCT instrument used 22 . In order to be visually discerned, the signal differences must be at least three to five times greater than the noise (standard deviation) in the image 51 .…”

“…In the context of earlier work by Ashton et al 22 and of this present, it is noteworthy that MicroCT in conjunction with iodinated contrast agent can provide an alternative and non-destructive method of determining infarct size longitudinally.…”

“…Newer small animal studies reduced the gap between MicroCT and SPECT, the modality of choice for perfusion and viability assessment 22 . With the goal to evaluate the degree of regional blood flow impairment caused by the LAD coronary artery occlusion, the MicroCT data were also evaluated for myocardial perfusion information.…”

“…In addition to their better safety profile, these contrasts are taken up by metabolically active tissues, thus can be used for viability assessment 22,23 . To this end, iodinated contrast agent was selected for the present study.…”

“…Thus, such MicroCT instruments can be well suited for routine examination of small animals as models of human disease. Most importantly, with the development of a novel preclinical iodinated contrast agent, simultaneous functional and metabolic assessment of the heart became possible [22][23][24] .…”