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In Vivo Quantification of Myocardial Infarction in Mice Using Micro-CT and a Novel Blood Pool Agent
时间:2017-10-24 12:39   来源:未知   作者:admin   点击:
       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 (). Thus, the developed micro-CT method allows for monitoring of a variety of processes such as cardiac remodeling in longitudinal studies.
1. 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. However, it is a fact that the acquisition time in typical micro-CT devices is significantly higher than those of clinical devices. Indeed, 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. Due to the rapid clearance of clinical CT contrast agents from the blood pool of small animals, clinical agents are not optimal for small animal imaging [1, 2]. In fact, when using clinical CT contrast agents in micro-CT studies, the data acquired is inconsistent and image reconstruction is only possible using sophisticated injection protocols [3]. 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.
       Currently, there are a handful of commercially available micro-CT blood pool agents, which find application in vessel imaging, liver and spleen imaging, and cardiac imaging [4–11]. In view of cardiac imaging, for example, in studies of cardiac infarction and remodeling, the prolonged blood circulation time of micro-CT blood pool agents renders assessment of morphological and functional cardiac parameters possible. Besides their long blood half-life, these agents preferably create a high contrast between the blood and the myocardium at a low injection volume. Due to the inherently low blood volume of small animals, low injection volumes are desired so as to minimize adverse haemodynamic effects. Furthermore, in cardiac micro-CT studies, the animal models, for example, model for myocardial infarction, tend to be susceptible to volume overload. Thus, for cardiac imaging, a blood pool agent with a high concentration of the signal-enhancing moiety is preferred, allowing for high contrast at low injection volume.
       Owing to the high cardiac rate (about 600 beats/min) and rapid respiratory rate (about 300 breaths/min) of small animals, cardiac micro-CT requires the application not only of high-contrast blood pool agents but also of reconstruction methods that allow significant reduction of motion artifacts. While it is indisputable that cardiac parameters can be obtained using positron emission tomography (PET), single photon emission computed tomography (SPECT), or magnetic resonance imaging (MRI), micro-CT reconstruction methods provide images with superior spatial and temporal resolution [12–15].
       In this study, 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. Through measurement of the infarct volumes observed on the micro-CT reconstructions and comparison with the volumes obtained from histopathology, we assess the feasibility of the method to noninvasively monitor cardiac processes and pathologies in small animals.


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