## 3 FF-OCT and Histology Contrasts
To completely remove slicing artifacts and reach large depths, OCT systems have successfully been coupled to a vibratome, in a procedure where an entire volume is imaged before a physical slice smaller than the imaged volume is performed [59]. Additionally, OCT systems capture the light naturally backscattered by the sample, without using any label. Working label-free can be advantageous, as staining artifacts can be avoided, and as it can importantly reduce the time prior to imaging. On the other hand, the recorded signal often lacks specificity. The obtained contrast is complicated to predict, as it is described by multi-scale complex theories, notably combining Rayleigh and Mie theories, depending on the scatterer size [60]. However, for a given tissue, the obtained contrast is highly reproducible, so the diagnosis performance could be increased only by simply better characterizing the typical contrast obtained on each tissue, and each condition. Quite generally, we can nevertheless emphasize the strong ability of FF-OCT to detect high refractive index (high lipid or high fat content) fibers, such as collagen fibers [8], myelin fibers [61], and even some large unmyelinated axons in the eye [62]. Moreover, in terms of contrast, looking at the backscattered light can differ substantially from transmission microscopes in thick samples. However, one can assume that for thin slices, the contrast in reflection is mainly the inverted contrast for scattering structures and the same contrast from absorbing structures compared to a transmission microscope. The label-free ability of OCT has a final practical advantage, since the imaging can be performed prior to any tissue modification. It means that the same tissue can be further used for another procedure, including a standard histology procedure [8], or fluorescence labeling. It is usually preferred to perform the OCT imaging before any sample modification, as OCT signal alteration can occur after fixation, depending on the tissue content [62] (especially since fixatives often remove lipidic structures of the cells). Keeping this in mind, it is nevertheless possible to perform histology-like measurements in fixed tissues [58]. Scanning OCT has also been used successfully to perform histology-like measurements [58; 63; 64; 65], and to detect tumor regions [66; 67] through changes in the collagen content [68], the tissue microangiogram and backscattering [69], or in the tissue fractal dimension [70]. However, we believe that the high resolution of FF-OCT can significantly improve the diagnostic abilities of OCT [8; 17]. With higher numerical apertures, the light collection is improved which helps to reveal more structures and increase the signal-to-noise ratio for the calculation of backscattering coefficients or fractal dimensions [40; 71]. Signal from cell contours and from intracellular structures can also be detected. This will be described in Section 5 on Dynamic FF-OCT. Finally, the _en face_ view of the sample is quite natural for histologists, as it looks similar to histology slides. FF-OCT is also faster than scanning OCT to record a single _en face_ image. Figure 2 shows a comparison between FF-OCT and a regular H & E histology in a breast sample, the organization of which is altered by a ductal carcinoma in situ (DCIS). FF-OCT notably reveals normal adipocytes, normal and abnormal collagen fibers (based on their scattering strength), and enlarged ducts. These indicators are characteristics of DCIS, that could be identified with 90% sensitivity and 75 % specificity in this case [14].