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

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.

Mouse Models of Heart Failure with Preserved or Reduced Ejection Fraction

“…Coronary artery ligation is the most common mouse model used to mimic myocardial infarction (MI). 46 Ligation of the left anterior descending artery results in HF, with HFrEF developing by 6 weeks after infarction. Myocyte death and extracellular matrix deposition leading to a collagenous scar can be assessed by Evans Blue and 2,3/5-triphenyltetrzolium chloride double staining, where the typical infarct area is between 50% and 60% of the total LV wall area.…”

Emerging methods for the characterization of ischemic heart disease: ultrafast Doppler angiography, micro-CT, photon-counting CT, novel MRI and PET techniques, and artificial intelligence

“…Its accumulation in the healthy myocardial tissue combine with its long blood half-life (about 2 h in mice) allows for visualizing myocardial pathological changes as well to perform functional cardiac imaging [ 27 ]. This agent has been tested in micro-CT to longitudinally monitor cardiac processes in vivo, in mice with myocardial infarction [ 28 ]. ExiTron MyoC 8000-enhanced micro-CT imaging was able to detect and accurately quantify myocardial infarction, even at a very low contrast dose (50 μL per 25-g mouse body weight, 210 mg I/mL).…”

Nanoparticles for diagnosis and therapy of atherosclerosis and myocardial infarction: evolution toward prospective theranostic approaches

“…Recently, Sawall et al developed a pre-clinical micro-CT method using a contrast agent based on nanocapsules with high iodine concentration (ExiTron TM MyoC 8000) to longitudinally monitor cardiac processes in vivo in healthy and MI-inflicted mice 81 . The study also evaluated nanoparticles of high alkaline-earth metal content (ExiTron TM nano) 81 . Due to its ability to be taken up by infarct myocardium but not by healthy tissue, ExiTron MyoC 8000 enabled detection of MI even at a very low dose.…”

“…The signal enhancement after contrast agent injection was exploited for quantification of infarct size. Thus, the developed micro-CT method allowed monitoring of a variety of processes such as cardiac remodeling in longitudinal studies 81 . In another study, Cormode et al used AuNPs with an iodinated contrast agent in a new prototype spectral photon-counting computed tomography (SPCCT) system 82 .…”