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Heating can enhance gene transfection/expression. We developed a novel endovascular microwave heating source using an MR imaging-guidewire (MRIG) to deliver external microwave energy into the target vessels. We investigated (i) microwave power loss along differently-sized MRIGs; (ii) microwave power distribution around MRIGs; and (iii) temperature increases versus input microwave powers with MRIGs. Then, we evaluated, in vivo, the possibility of using the MR imaging/heating guidewire to generate high-resolution MR images and deliver the controlled therapeutic heat energy into the target vessel wall with histological confirmation. The results showed that the MRIG had no thermal damage to the vessel wall and can be used as an intravascular local heating device. This study has established the groundwork for further efficient management of cardiovascular atherosclerotic diseases using MRI-based vascular gene therapy.