Magnetic resonance fluoroscopy allows targeted delivery of mesenchymal stem cells to infarct borders in swine

• Published in: Circulation (New York, N.Y.) Vol. 108; no. 23; pp. 2899 - 2904
• Main Authors: DICK, Alexander J, GUTTMAN, Michael A, RAMAN, Venkatesh K, PETERS, Dana C, PESSANHA, Breno S. S, HILL, Jonathan M, SMITH, Scott, SCOTT, Greig, MCVEIGH, Elliot R, LEDERMAN, Robert J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 09-12-2003; American Heart Association, Inc
• Subjects: Animals; Biological and medical sciences; Blood and lymphatic vessels; Cardiac Catheterization; Cardiology. Vascular system; Computer Systems; Contrast Media; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Feasibility Studies; Ferrosoferric Oxide; Gadolinium DTPA; Imaging, Three-Dimensional; Iron; Magnetic Resonance Imaging - instrumentation; Magnetic Resonance Imaging - methods; Medical sciences; Mesenchymal Stem Cell Transplantation - methods; Microscopy, Fluorescence; Microspheres; Myocardial Infarction - pathology; Myocardial Infarction - therapy; Oxides; Phantoms, Imaging; Safety; Swine, Miniature; Transplantation, Homologous; magnetic resonance imaging; cells; Radiodiagnosis; drugs; Stem cell; Magnetic resonance; myocardial infarction; Radioscopy; Cardiovascular disease; catheterization; Target cell
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000095790.28368.F9

The local environment of delivered mesenchymal stem cells (MSCs) may affect their ultimate phenotype. MR fluoroscopy has the potential to guide intramyocardial MSC injection to desirable targets, such as the border between infarcted and normal tissue. We tested the ability to (1) identify infarcts, (2) navigate injection catheters to preselected targets, (3) inject safely even into fresh infarcts, and (4) confirm injection success immediately.
A 1.5-T MRI scanner was customized for interventional use, with rapid imaging, independent color highlighting of catheter channels, multiple-slice 3D rendering, catheter-only viewing mode, and infarct-enhanced imaging. MRI receiver coils were incorporated into guiding catheters and injection needles. These devices were tested for heating and used for targeted MSC delivery. In infarcted pigs, myocardium was targeted by MR fluoroscopy. Infarct-enhanced imaging included both saturation preparation MRI after intravenous gadolinium and wall motion. Porcine MSCs were MRI-labeled with iron-fluorescent particles. Catheter navigation and multiple cell injections were performed entirely with MR fluoroscopy at 8 frames/s with 1.7x3.3x8-mm voxels. Infarct-enhanced MR fluoroscopy permitted excellent delineation of infarct borders. All injections were safely and successfully delivered to their preselected targets, including infarct borders. Iron-fluorescent particle-labeled MSCs were readily visible on delivery in vivo and post mortem.
Precise targeted delivery of potentially regenerative cellular treatments to recent myocardial infarction borders is feasible with an MR catheter delivery system. MR fluoroscopy permits visualization of catheter navigation, myocardial function, infarct borders, and labeled cells after injection.