In Vivo Magnetic Resonance Imaging of Catheter-Based Vascular Gene Transfer

The purpose of this study was to develop an in vivo imaging tool to monitor vascular gene transfer. We produced gadolinium/blue-dye and gadolinium/gene-vector media by mixing Magnevist with a trypan-blue or a lentiviral vector carrying a green fluorescent protein (GFP) gene. The gadolinium was used as an imaging marker for MRI to visualize vessel wall enhancement, while the blue-dye/GFP was used as a tissue stain marker for histology/immunohistochemistry to confirm the success of the transfer. Using Remedy gene delivery catheters, we transferred the gadolinium/blue-dye (n=8) or gadolinium/GFP-lentivirus (n=4) into the arteries of 12 pigs, monitored under high-resolution MR imaging. This technical development enabled dynamic visualization of: (i) where the gadolinium/genes distributed; (ii) how satisfactorily the target portion was marked; and (iii) whether the gene transfer procedure caused complications. Our study represents the first direct evidence that catheter-based vascular gene delivery/distribution can be monitored by MR imaging in vivo. Key wards: cardiovascular disease, magnetic resonance imaging, vascular gene therapy