## 4 Discussion  
The post-mortem assessment of amyloid-beta plaques is an essential component of neuro-pathological AD diagnostics [16]. In this article, we investigated the imaging capabilities of OCT intensity and polarization contrast as alternative techniques for the visualization and quantitative assessment of amyloid-beta plaques in ex-vivo cerebral tissue of AD patients. PS-OCT visualizes amyloid-beta plaques based on their optical scattering and birefringent properties [33; 34; 35; 36]. Previous studies mainly exploited the hyperscattering characteristics of plaques and only one report investigated the birefringent characteristics of neuritic plaques using PS-OCT [19]. Here, we presented a comparative analysis of the plaque visualization capabilities of intensity- and PS-OCT contrast. Surprisingly, most plaques appeared in only one contrast channel and were in most of the cases not visible in the other. While for each patient, we observed different fractions of plaques in intensity and retardation respectively (Figure 4), only very few plaques--on average 5%--did actually overlap (Figure 2). This finding may indicate different underlying contrast mechanisms, suggesting that distinct subgroups of plaques provide independent optical contrast. Figure 7 may suggest that intensity and retardation contrasts visualize different plaque morphologies. However, further investigation and a one-on-one correlation to histology would be required in order to elucidate the relationship between the two OCT contrast channels with the different subgroups of plaques. In our earlier work, we simulated the birefringent [19] and scattering signals [36] produced by neuritic plaques assuming a geometry of radiating fibrils [43]. These simulations suggested that neuritic plaques are birefringent, resulting in increased phase retardation observed in PS-OCT [19]. As cumulative phase retardation effects occur, some plaques exhibit retardation trails. In our recently published simulations we found that low numerical aperture (NA) values resulted in straight retardation shadows in z-direction whereas higher NA values produced a lateral spread of those shadows [19]. The intensity of directly backscattered light was found to be rather low for this plaque geometry, such that strong neuritic plaque signals were only observed using a dark-field detection scheme for OCT [36]. By analyzing the signal levels in plaques compared to the surrounding gray matter, most birefringent plaques (i.e., those visualized in retardation images) were invisible in co-localized OCT intensity data. However, higher retardation was observed only in these birefringent plaques as compared to those highlighted in the intensity images. This finding, which is also supported by previous research reporting the visualization of plaques by OCT without polarization contrast [31; 32; 33; 34; 35], reinforces our assumption that intensity and retardation-based contrasts are caused by different families of amyloid-beta plaques. To further evaluate this, WC and SNR calculations were performed. As Figure 3 shows, there was no significant difference either in WC or SNR when comparing intensity  
Figure 7: Comparison of histology and OCT data. (**a**) Absolute plaque count (p/mm\({}^{2}\)) in retardation and intensity data including those which overlap, compared to diffuse and dense plaques in histology. (**b**) Histogram of the plaque diameter in dense (4.8–25.5 \(\upmu\)m) and diffuse plaques (6.9–83.6 \(\upmu\)m) evaluated in histological slices. (**c**) A typical image of a dense plaque. (d) A typical image of a diffuse plaque. data. This slight difference may be explained by a depth-dependent contrast increase between plaques and surrounding brain parenchyma. However, note that plaques vary not only in size but also in shape and density. Therefore, in intensity images, many plaques appeared as strong hyperreflective spots and only some expressed a vague hyperreflectivity, resulting in weaker WC and SNR values. For retardation images, WC differences were significant.