Microstructural Impact of Ischemia and Bone Marrow-Derived Cell Therapy Revealed with Diffusion Tensor MRI Tractography of the Heart In Vivo
Background—The arrangement of myofibers in the heart is highly complex and must be replicated by injected cells to produce functional myocardium. A novel approach to characterize the microstructural response of the myocardium to ischemia and cell therapy, using serial diffusion tensor MRI (DTI) tractography of the heart in vivo, is presented.
Methods and Results—Validation of the approach was performed in normal (n=6) and infarcted mice (n=6) as well as healthy human volunteers. Mice (n=12) were then injected with bone marrow mononuclear cells (BMMCs) 3 weeks after coronary ligation. In half the mice the donor and recipient strains were identical and in half the strains were different. A positive response to cell injection was defined by a decrease in mean diffusivity, an increase in fractional anisotropy, and the appearance of new myofiber tracts with the correct orientation. A positive response to BMMC injection was seen in one mouse. The response of the majority of mice to BMMC injection was neutral (9/12) or negative (2/12). The in vivo tractography findings were confirmed with histology.
Conclusions—DTI-tractography was able to directly resolve the ability of injected cells to generate new myofiber tracts and provided a fundamental readout of their regenerative capacity. A highly novel and translatable approach to assess the efficacy of cell therapy in the heart is thus presented.
- Received August 21, 2013.
- Revision received January 29, 2014.
- Accepted January 31, 2014.