Tissue visualization device and method variations are 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 translucent or transparent fluid is pumped into the hood until the fluid displaces any blood leaving a clear region of tissue to be imaged via an imaging element. Temporary sealing against the tissue can be achieved in a number of ways such as circumferential balloons inflatable within the hood or other sealing techniques. A field of view of the imaging element can be expanded by inflating the balloon beyond the imaging hood.