Tissue visualization device having a fluid barrier is described herein where an imaging hood is temporarily sealed against a region of tissue to be treated while under direct visualization. Such a system may include a deployment catheter and an attached imaging hood deployable into an expanded configuration. The imaging hood is placed against or adjacent to the tissue to be imaged in a body lumen that is normally filled with an opaque bodily fluid such as blood. A field of view of the imaging element can be expanded and the blood can also be purged in part by inflating a balloon beyond the imaging hood where the balloon is integrally formed along an interior surface of the hood.