Critically evaluating the methodology of the adventitial delivery of stem cells, some specific options should be underlined. Adventitia as the most superficial layer, consisting of connective tissue has to be distinguished of perivascular tissues. By strict definition, an adventitia is the outermost connective tissue covering any organ, or vessel. The "adventitial" delivery of stem cells with a 1 mm micro-needle means a delivery to superficial so called pericardial myocardium, perivascular fat tissues, including a risk of perforation and injury of soft tissues. In fact, the mapping of the artery with visualization of the three-layer vessel structure and perivascular tissues as well as pericardial space with the state-of-the-art imaging approaches including IVUS (intravascular ultrasound) or OCT (optical coherence tomography) allows to find an optimal site for injection, prevents any technical complications and improves efficacy. NOGA magnetic navigation system still remains the optimal tool for the stem cell delivery to myocardium with appropriate visualization of necrosis and peri-infarct tissues. Potentially, more advanced imaging provides a chance to deliver infusate to the adventitial layer, which is a gate to the vessel wall for inflammation as well as a source of stem and progenitor cells, and myofibroblasts. (C) 2012 Elsevier Ireland Ltd. All rights reserved.