Evaluation of Novel Therapeutics

Mouse models of cardiovascular disease are ideal for the evaluation of novel therapeutic interventions. Our small-animal imaging group is involved in several studies of novel therapies in mouse and rat models of cardiovascular disease. We have a particular interest in the evaluation of experimental therapies for myocardial dysfunction and heart failure. MRI is the ideal tool with which to evaluate such therapies, providing both high-resolution anatomical and functional information. The location of our group at the Massachusetts General Hospital provides the ideal environment to interact with leaders in the field of cutting-edge cardiovascular therapies. Two of our closest collaborators, Dr. Anthony Rosenzweig and Dr. Roger Hajjar, are world recognized experts in this field and are responsible for convening a NIH-sponsored international conference in Cardiovascular Cell and Gene Therapy every two years in Boston. Selected examples of current areas of investigation in our group are provided below:

1. Evaluation of novel cardio-protective mechanisms in mouse models of ischemia, acute infarction and reperfusion injury:

Despite dramatic advances in the treatment of the acute coronary syndromes many patients still suffer significant myocardial damage during these events.  In collaboration with the laboratory of Dr. Anthony Rosenzweig, Director of the MGH Program in Cardiovascular Gene Therapy, we are using cardiac MRI to evaluate the impact of novel cardio-protective strategies in mouse models of ischemia, myocardial infarction and reperfusion injury.

2. Evaluation of stem cell therapy in a mouse model of chronic myocardial infarction:

There is currently significant interest in the use of mesenchymal stem cells to regenerate non-viable, scarred myocardium. However, it is still not fully known whether stem cells are able to survive and establish functional electro-mechanical connections in the hypoxic nutrient-deprived milieu of myocardial scar. There is thus significant interest in the development of imaging tools that allow injected stem cells to be tracked in the myocardium. Our group has recently become involved in the use of MRI to track labeled stem cells injected into mouse infarcts. This work is being conducted in collaboration with Dr. Anthony Rosenzweig’s and Dr. Roger Hajjar’s laboratories. In addition to allowing injected stem cells to be tracked, MRI enables myocardial function and morphology in the area of the stem cell injection to be monitored with a high degree of accuracy. 

Figure 2: Iron-oxide labeled stem cells injected into the antero-lateral wall of the left ventricle. Gradient echo MR images with echo times of 2.7 ms (panel A) and 4.7 ms (panel B) are shown. A signal void (white arrows) is seen in the region of the stem cell injection. Prussian Blue staining (panels C, D) confirm the presence of  iron in the region of the signal void.