Systems and methods are provided for injecting one or more agents into tissue within a patient's body that includes a catheter. A needle guide extends from a distal end of the catheter and terminates at a distal tip, e.g., including a foot with an atraumatic contact surface, the needle guide having a cross-section smaller than the distal end and being biased to a curved shape. The needle guide includes a passage communicating from a lumen of the catheter to an outlet at the distal tip, and a needle device is disposed within the passage that may be deployed from the outlet to inject one or more agents into tissue. The catheter also includes an imaging assembly on the distal end configured to acquire images of tissue adjacent the needle guide distal tip.