In Vivo Quantification of Myocardial Infarction in Mice Using Micro-CT and a Novel Blood Pool Agent.

Stefan Sawall,Jan Kuntz,Marc Kachelrieß,Jan Beckendorf,Alexander Kraupner,Danielle Franke,Johannes Backs,Andreas Briel,Joscha Maier,Anne Kirchherr

doi:10.1155/2017/2617047

Abstract

We herein developed a micro-CT method using the innovative contrast agent ExiTron™ MyoC 8000 to longitudinally monitor cardiac processes in vivo in small animals. Experiments were performed on healthy mice and mice with myocardial infarction inflicted by ligation of the left anterior descending artery. Time-dependent signal enhancement in different tissues of healthy mice was measured and various contrast agent doses were investigated so as to determine the minimum required dose for imaging of the myocardium. Due to its ability to be taken up by healthy myocardium but not by infarct tissue, ExiTron MyoC 8000 enables detection of myocardial infarction even at a very low dose. The signal enhancement in the myocardium of infarcted mice after contrast agent injection was exploited for quantification of infarct size. The values of infarct size obtained from the imaging method were compared with those obtained from histology and showed a significant correlation (R2 = 0.98). Thus, the developed micro-CT method allows for monitoring of a variety of processes such as cardiac remodeling in longitudinal studies.

Highlights

The introduction of micro-CT has brought about considerable improvements in anatomical imaging of small animals through the modality’s high spatial resolution that enables identification of morphological changes in small structures
We develop a micro-CT method using the innovative micro-CT blood pool agent ExiTron MyoC 8000, having a high iodine concentration (210 mg I/mL), to longitudinally monitor cardiac function in a mouse model of myocardial infarction
In order to investigate the kinetics of ExiTron MyoC 8000, signal enhancements, that is, baseline-corrected CT-values, in tissues of healthy mice were measured over a period of 250 min after injection of the contrast agent at a dose of 1050 mg I/kg body weight with an additional scan after 24 h (Figure 1)

Summary

Introduction

The introduction of micro-CT has brought about considerable improvements in anatomical imaging of small animals through the modality’s high spatial resolution that enables identification of morphological changes in small structures. Whereas a clinical scan may take even less than one second, a micro-CT scan requires around 30 min and, at times, may even take up to 1 h. Such long scan times necessitate the use of a contrast agent that is not rapidly cleared from the animal but, instead, persists in the blood for a prolonged period of time. To overcome the issue of rapid contrast agent clearance, micro-CT investigations are generally coupled with blood pool contrast agents, which persist in the blood for a prolonged period of time

Methods

Results

Conclusion