The imaging system with micron-class resolution of 2 μm axially and laterally in skin tissue consists of a Titanium:Sapphire femtosecond laser centered at 800 nm with 120 nm full width half maximum (FWHM) (Integral, Femtolasers, Inc.), a custom liquid-lens-based 3-D scanning microscope,38 a broadband custom-made fiber coupler (NSF-DARPA/PTAP), a custom dispersion compensator,39 and a custom spectrometer with a high-speed CMOS line camera (spl8192-70 km, Basler Inc).40 To achieve the axial resolution of 2 μm using a 1050 or 1300 nm source, a bandwidth of 207 nm FWHM or 316 nm FWHM would be required, respectively. The extended bandwidth would limit the selection of an appropriate source, spectrometer, and optics. In addition, it would be more difficult to compensate the overall dispersion to secure the resolution in a fiber-based system. To achieve 2-μm lateral resolution, a relatively lower NA of the objective is needed with a wavelength of 800 nm compared with the wavelengths 1050 and 1300 nm. At constant lateral resolution, the depth of focus decreases as the inverse of the wavelength. Therefore, using a longer wavelength also gives the challenge of needing more zones in depth, which will limit the overall imaging speed. Although OCT at 1050 or 1300 nm gets deeper imaging compared with OCT at 800 nm, the latter can obtain relatively high speed imaging at 2-μm resolution over 500 μm deep, which is sufficient to image the epidermis ( for facial skin) where skin cancer generally develops. Spectra were acquired with an exposure time of 48 μs and a readout speed of . We acquired six volumes from the same portion of a skin tissue with a sampling interval of 1 μm for 10 min, which corresponds to a total of Ascans spectra. The six volumes were taken relative to a shifted focal plane with 100 μm separation. Using the 100 μm separation between focal planes, over a depth of 60 μm there is 2-μm lateral resolution, and the remaining imaging depth (i.e., 40 μm) supports 3-μm lateral resolution measured as a minimum of 20% contrast criterion.41 The lateral scale of images was determined with the scanned length by the two galvanometer based mirrors. The optical depths () of the structure were first measured with optical path differences between the reference arm and the structures in the sample and the optical depths were then rescaled to the physical depths of the images by dividing them with the average refractive index 1.4 of epidermis and dermis at 800 nm.42 The six volume images were reconstructed in post-processing into one volume using the Gabor-based fusion technique.37 All acquisition and post-processing including interpolation, fast Fourier transform, and fusion were done using Labview software that was run on a PC equipped with a 64-bit processor and Windows 7 operating system to secure sufficient computer memory.