Serial in vivo positive contrast MRI of iron oxide-labeled embiryonic stem cell-derived cardiac precursor cells in a mouse model of myocardial infarction

Myocardial regeneration with stem-cell transplantation is a possible treatment option to reverse deleterious effects that occur after myocardial infarction. Since little is known about stem cell survival after transplantation, developing techniques for tracking cells would be desirable. Iron-oxide-labeled stem cells have been used for in vivo tracking using MRI but produce negative contrast images that are difficult to interpret. The aim of the current study was to test a positive contrast MRI technique using reduced z-gradient rephasing (GRASP) to aid in dynamically tracking stem cells in an in vivo model of mouse myocardial infraction. Ferumoxides and protamine sulfate were complexed and used to magnetically label embryonic stem cell-derived cardiac-precursor-cells (ES-CPCs). A total of 500,000 ES-CPCs were injected in the border zone of infarcted mice and MR imaging was performed on a 9.4T scanner using T-2*-GRE sequences (negative contrast) and positive contrast GRASP technique before, 24 hours, and 1 week after ES-CPC implantation. Following imaging, mice were sacrificed for histology and Perl's staining was used to confirm iron within myocardium. Good correlation was observed between signal loss seen on conventional T-2* images, bright areas on GRASP, and the presence of iron on histology. This demonstrated the feasibility of in vivo stem cell imaging with positive contrast MRI.