Methods, systems and devices for delivering a diagnostic or therapeutic treatment, substance or device to a target area located within the body of a human or animal subject. A tissue penetrating catheter is positioned within a body lumen near the target area. A hollow penetrator is then advanced from the tissue penetrating catheter and penetrated from the body lumen in which the penetrating catheter is positioned into tissue in the direction of the target area. Thereafter, an elongate optical device (e.g., an optically equipped guidewire or catheter) is advanced through the hollow penetrator and continues to advance through tissue, in the direction of the target area. The elongate optical device is connected to an optical processing device (e.g., a spectrometer) which provides optically determined data (e.g., spectral reflectance, pH, oxygen concentration, temperature) indicating when the elongate optical device has entered the target area. The elongate optical device is then used to facilitate delivery of a diagnostic or therapeutic modality, substance or device into the target area.