Introduction and Hypothesis:
The prevalence of myocardial infarction increases with the average age of the population and is currently the leading cause of death worldwide. In order to define anatomical changes and biomarkers related to cardiac infarction, we tested the use of combined computed tomography (CT) and near infrared fluorescent (NIRF) probes to facilitate non-invasive imaging of processes concerned with tissue degeneration/regeneration. This development of new non-invasive diagnostic methods will lead to better treatment options in the future.
Methods:
Mice were subjected to left anterior descending artery (LAD) ligation inducing an acute myocardial infarction and subsequently imaged
in vivo
using
fast
and
low dose
microCT scanning (QuantumFX, Perkin Elmer) and near infrared (NIRF) probes to monitor MMP activity (MMPsense680). Immediate contrast enhanced CT imaging using eXIA160 during its blood-pool phase allowed registration of changes in ventricular anatomy and function of important global parameters, like end-diastolic volume (EDV), end-systolic volume (ESV). These were used to calculate stroke volume (SV), and left ventricular ejection fraction (LVEF). Delayed eXIA160 contrast uptake during its myocardial phase, subsequently allowed analysis of the infarct size and infarct healing. In addition,
in vivo
molecular MMPsense localization was combined with micro-CT imaging for accurate 3D co-registration.
Results:
Changes in ventricular anatomy and myocardial viability were assessed 3 hours and 2 months post LAD occlusion in the same animal, demonstrating the feasibility of monitoring myocard viability over time. The decreased uptake of eXIA160 in the myocardium was subsequently quantitated. A concomitant increase in MMP activity, as determined by fluorescence mediated tomography using MMPsense680, could be localized to the infarcted site.
Conclusions:
Non-invasive imaging, using NIRF probes, enables longitudinal imaging of processes concerned with myocard infarction. Consequently, disease progression can be monitored over time and the effect of (new) pharmacotherapy can be studied.
Evaluation of spectral photon counting computed tomography K-edge imaging for determination of gold nanoparticle biodistribution in vivo
