Abstract: An apparatus for treating tissue includes a flexible catheter including a proximal end, a distal end for introduction into a chamber of a heart, a transparent balloon carried by the distal end, an optical imaging assembly carried by the distal end for imaging tissue structures beyond the distal end through the balloon, and a needle deployable from the tubular member for penetrating the tissue structure to treat tissue. The apparatus may include a source of stems cells or other therapeutic and/or diagnostic agent coupled to the needle, a guide catheter advanceable over the needle for accessing a region beyond the tissue structure penetrated by the needle, and/or an energy probe deployable from the catheter for delivering electrical energy to tissue in the region beyond the tissue structure. The apparatus may be used to deliver stem cells into infracted tissue or for ablating heart tissue, e.g., from a trans-septal approach.