## 3 FF-OCT and Histology Contrasts  
In order to further compare histology and FF-OCT, we describe in this section histology contrast and procedures. It is commonly said that [PERSON] is the precursor of modern histology, as he was the first scientist to carefully describe micro-anatomic features of plants and animal tissues by the end of the 17 th century with the first microscopes [48; 49]. Since then, histology has continuously benefited from advances in chemical labeling and fixatives, and has benefited from a better understanding of tissue nanostructures and organization thanks to electron microscopy [50]. It now benefits from an extensive literature, and from digital atlases [51; 52; 53] enabling direct comparisons with normal or pathological slices of most tissues. However, the basic microscopy principles have mainly remained unchanged since the beginning of histology. They consist of imaging a thin slice of a sample with a simple transmission optical microscope. Since light absorption and scattering by biological structures exhibit a low contrast, histology commonly uses chemical agents to reveal specific contrasts of interest [54; 55; 56]. The most common staining uses two associated stains, Hematoxylin and Eosin (H & E), that respectively label chromatin and chromosomes in blue, and cytoplasm in red. Hemoglobin usually appears orange, and collagen fibers appear pink. This staining is particularly versatile, as it can be used with a variety of fixatives. A wide range of different staining can be applied to a tissue slice. We can non-exhaustively evoke Golgi staining that labels 1% to 2% of neurons with silver that absorbs light to appear dark, Nissl staining that labels nucleic acids, or tetraoxide osmium that labels unsaturated lipids and lipoproteins. If many subcellular structures can be selectively labeled, it is often difficult to combine different stains in a single slide. However, using specific labels imposes a prior knowledge of the tissue composition, and of the pathology, and some unlabeled biomarkers could be missed. Moreover, histology requires tissue fixation, performed either chemically or by freezing the sample, and physical slicing of the tissue, usually performed by a microtome. The fixation first goal is to harden the sample to be able to cut it in thin sections. However, fixation can introduce strong artifacts, as it often removes lipidic structures, and can increase the tissue volume. The physical slicing can induce physical damage, notably in neuronal tissues, in which many axial neurites are usually cut, leading to neuronal death. Finally, these two steps are usually time consuming, and can lead to the physical destruction of the samples if not adequately performed. In the case of histopathology, the tissue is often fixated by replacing water by paraffin, and is then sliced in 4 to 5 \(\upmu\)m slices. For each slice, the dyes have then to diffuse through the paraffin scaffold. In total, these processes can last for a few days. In the case of intra-operative histology, the time allowed to the pathologist is usually not more than 15 to 30 min. To meet these time requirements, the sample is frozen, and directly sectioned and colored. However, many tissues, such as fat, brain, or retina, are not well suited for this process, and the number of available labeling is limited. On the other hand, OCT was only invented 25 years ago, and its full-field version is 18 years old, so comparatively little literature and atlases can be found [57]. However, OCT and FF-OCT provide a label-free, and optically-sectioned imaging. This means that imaging can be performed right after tissue extraction, which can provide a very fast diagnosis, and could even ideally provide an intra-operative diagnosis to efficiently define a tumor margin for example. The main advantage of OCT is its virtual sectioning ability, enabling imaging at a few hundred microns below the tissue surface, hence reasonably far from the sectioned surface no matter which section is required [58].