Navigational imaging system and method for use in branched luminal structure. Flexible, spatially steerable probe is equipped with forward- and side-imaging mutually complementing means to enable sub-surface imaging, quantitative determination of probes positioning with respect to anatomical identifiers of structure, forming 3D image of structure in a volume defined by the imaging means, and positioning of probe in registration with a 3D coordinate system that is independent from the structure. Method includes determining anatomical identifiers of luminal structure branches based on 3D and sub-surface images, assigning such identifiers as fiducial points, and correlating the determined identifiers with those obtained from anatomical model to select target branch for further steering the probe. Optionally, data representing a distance between a branch of lumen from fiducial point and angular orientation of the branch is extracted from complete 3D and quantitative image of lumen obtained during a pull-back of probe along the lumen.
