Catheter devices, systems and methods for penetrating from one location within a patient's body to another location. An elongate catheter (12) is insertable into a natural or man-made lumen within the body of a patient. A penetrator (30) is advanceable from the catheter (12) to a target location outside of the lumen in which the catheter (12) is positioned. An optical imaging or tissue characterization apparatus (100) (e.g., an optical coherence tomography apparatus) is useable to image the anatomy and/or sense variables within tissue so as to locate the target location relative to indicia of the trajectory on which the penetrator (30) will advance from the catheter. The operator may then adjust the position and/or rotational orientation of the catheter (12) such that when the penetrator (30) is subsequently advanced, the penetrator (30) will enter the target location.