Utility of Dual-modality Bioluminescence and MRI in Monitoring Stem Cell Survival and Impact on Post Myocardial Infarct Remodeling

• Published in: Academic radiology Vol. 18; no. 1; pp. 3 - 12
• Main Authors: Zhang, Hualei, BS, Qiao, Hui, MD, PhD, Bakken, Ashley, BS, Gao, Fabao, MD, PhD, Huang, Bin, MD, Liu, Yingqiu Y., MS, El-Deiry, Wafik, MD, PhD, Ferrari, Victor A., MD, Zhou, Rong, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2011
• Subjects: Animals; bioluminescence; Cell Survival; Contrast Media; Dextrans; Disease Models, Animal; embryonic stem cells; Female; firefly luciferase; Genes, Reporter; Luciferases, Firefly; Luminescent Agents; Luminescent Measurements - methods; Magnetic Resonance Imaging - methods; Magnetite Nanoparticles; MR imaging; Myocardial infarction; Myocardial Infarction - physiopathology; Radiology; Rats; Rats, Nude; Stem Cells - cytology; superparamagnetic iron oxide; Ventricular Remodeling; Myocardial infarction; MR imaging; bioluminescence; embryonic stem cells; firefly luciferase; superparamagnetic iron oxide
• ISSN: 1076-6332; 1878-4046
• DOI: 10.1016/j.acra.2010.09.006

Rationale and Objectives Firefly luciferase (Fluc) reporter gene is an authentic marker for surviving stem cells. However, it is unable to visualize the intramyocardial delivery of stem cells or their impact on cardiac function. The investigators demonstrate that bioluminescence imaging (BLI) combined with magnetic resonance imaging (MRI) allows better assessment of cell delivery and the impact on post–myocardial infarction remodeling. Materials and Methods Murine embryonic stem cells (0.3 million) were double-labeled with Fluc and superparamagnetic iron oxide particles and injected into the infarct border zone of athymic rat hearts. BLI and MRI were performed serially up to 2 months after injection, followed by immunohistochemistry. Results Dual-modality imaging was able to verify the initial intramyocardial delivery of the cells and their survival status. Over time, BLI signal increased in seven of nine hearts and disappeared in the other two hearts. The divergence of BLI signal over time was supported by MRI findings. Left ventricular ejection fraction and fractional shortening estimated by MRI suggested that cell engraftment mediated a positive impact on post–myocardial infarction remodeling. Two months after intramyocardial injection, superparamagnetic iron oxide–associated signals facilitated the localization of the injection site. Conclusions Dual-modality imaging has the unique ability to monitor cell delivery, survival status, graft morphology, and impact on post–myocardial infarction remodeling.