Technology Insight: In Vivo Cell Tracking by Use of MRI

Walter J Rogers; Craig H Meyer; Christopher M Kramer

Disclosures

Nat Clin Pract Cardiovasc Med. 2006;3(10):554-562. 

In This Article

Summary and Introduction

Animal studies have shown some success in the use of stem cells of diverse origins to treat heart failure and ventricular dysfunction secondary to ischemic injury. The clinical use of these cells is, therefore, promising. In order to develop effective cell therapies, the location, distribution and long-term viability of these cells must be evaluated in a noninvasive manner. MRI of cells labeled with magnetically visible contrast agents after either direct injection or local or intravenous infusion has the potential to fulfill this goal. In this Review, techniques for labeling and imaging a variety of cells will be discussed. Particular attention will be given to the advantages and limitations of various contrast agents and passive and facilitated cell-labeling methods, as well as to imaging techniques that produce negative and positive contrast, and the effect on image quantification of compartmentalization of contrast agents within the cell.

Cell transplantation is currently an area of intense investigation in cardiovascular medicine. The use of stem cells has potential for treating heart failure, mitigating postinfarction ventricular remodeling, and treating vascular injury. A need exists to serially image cells weeks to months after intravenous administration or direct injection into tissues, in order to track migration into the target tissue. Currently, cardiovascular cell-tracking studies are at the preclinical stage, whereas the number of clinical trials of stem cell therapies is increasing rapidly. Some success has been seen in preliminary human trials of stem cell therapy for left ventricular dysfunction after myocardial infarction with use of MRI to assess outcomes,[1] although other studies have been less positive.[2] In addition to allowing changes in left ventricular size and function after stem cell therapy to be followed, MRI offers the potential of tracking cells in vivo using innovative approaches to cell labeling and image acquisition.

MRI provides regional contrast based on differences in proton density, flow and biochemical structure, which alter regional signal intensity within acquired images, seen as either negative (dark) or positive (bright) signal. In order to improve contrast further, contrast agents, such as gadopentate dimeglumine, are used in most clinical cardiovascular examinations. In myocardial examinations, gadolinium-based contrast agents highlight regions of reduced perfusion, allowing identification of regions of ischemia in patients with coronary artery disease[3] or myocardial necrosis due to infarction.[4] In vascular examinations, contrast agents are used to increase the signal from blood and thus improve vessel visualization, and are commonly used for angiographic applications.[5] These low-molecular-weight agents are extravascular and distribute with blood flow, but provide no cell-specific or process-specific information; therefore, such agents are not useful for cell tracking. Despite these contrast agents' lack of specificity, however, they are useful clinically for the applications mentioned above.

Polysaccharide-coated iron oxide nanoparticles have been investigated because of their good inherent signal differentiation when studied with typical MRI pulse sequences and ability to be internalized by cells with phagocytic capacity. Although current limits of spatial resolution preclude direct visualization of individual unlabeled cells, methods of signal amplification with internalized contrast material increase the ability of MRI to detect small numbers of cells. This Review of cell tracking will address potential contrast agents, methods of cell labeling, and MRI methods for sensitive cell detection.

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