Forward-looking ultrasound transducers are positioned at the tip of a transseptal catheter to facilitate transseptal puncture and interventions within the left atrium, pulmonary veins and mitral valve. Catheter devices and systems are guided by forward-looking ultrasound or optical coherence tomography imaging for penetrating from one location within a mammalian patient's body to another location, and/or performing diagnostic or therapeutic interventions. A penetrator, diagnostic, or interventional device (eg. probe, biopsy apparatus, electrode, needle) is positioned at the catheter tip and is advanceable from the catheter to a target location outside of the lumen in which the catheter is positioned. The imaging probe uses forward-looking ultrasound or optical coherence tomography that allows one to locate both the target and the medical device. The operator may then adjust the position and/or rotational orientation of the catheter such that when the medical device is subsequently advanced it will either enter or be deployed at the target location.