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Am J Physiol Heart Circ Physiol (February 23, 2007). doi:10.1152/ajpheart.01307.2006
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Submitted on November 29, 2006
Accepted on February 17, 2007

High Resolution Imaging of Murine Myocardial Infarction With Delayed Enhancement Cine Micro-CT

Matthias Nahrendorf1*, Cristian Badea2, Laurence W Hedlund3, Jose-Luiz Figueiredo4, David E Sosnovik1, G. Allan Johnson5, and Ralph Weissleder1

1 Center for Molecular Imaging Research, Massachusetts General Hospital, Boston, Massachusetts, United States
2 Center for In Vivo Microscopy, Duke Medical Center, Durham, North Carolina, United States
3 Durham, North Carolina, United States; Center for In Vivo Microscopy, Duke Medical Center, Durham, North Carolina, United States
4 Center for Molecular Imaging Research, Massachusetts General Hospital, Boston, Massachusetts, United States; Boston, Massachusetts, United States
5 United States; Center for In Vivo Microscopy, Duke Medical Center, Durham, North Carolina, United States

* To whom correspondence should be addressed. E-mail: mnahrendorf{at}partners.org.

Objective: To determine the feasibility of delayed enhancement µCT imaging to quantify myocardial infarct size in experimental mouse models. Methods and Results: A total of 20 mice were imaged 5 or 35 days after surgical ligation of the left coronary artery, or sham surgery (n=6-7 per group). We utilized a prototype µCT which covers a 3D volume with an isotropic spatial resolution of 100 µm. A series of image acquisitions were started after a 200 µL bolus of a high molecular weight blood pool CT agent to outline the ventricles. CT imaging was continuously performed over 60 minutes, while an intravenous constant infusion with iopamidol 370 was started at a dosage of 1 mL/h. Thirty minutes after the initiation of this infusion, signal intensity in Hounsfild Units was significantly higher in the infarct than in the remote, uninjured myocardium. Cardiac morphology and motion was visualized with excellent contrast and in fine detail. In vivo CT determination of infarct size at the mid-ventricular level was in good agreement with ex vivo staining with triphenyltetrazolium chloride (5 days post MI: r2= 0.86, p < 0.01; 35 days post MI r2=0.92, p < 0.01). In addition, we detected significant left ventricular remodeling consisting of left ventricular dilation and decreased ejection fraction. Conclusion: 3D cine µCT reliably and rapidly quantifies infarct size and assesses murine anatomy and physiology after coronary ligation, despite the small size and the fast movement of the mouse heart. This efficient imaging tool is a valuable addition to the current phenotyping armamentarium and will allow rapid testing of novel drugs and cell based interventions in murine models.







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