Comparison of Intensity- and Polarization-based Contrast in Amyloid-beta Plaques as Observed by Optical Coherence Tomography

Abstract

One key hallmark of Alzheimer’s disease (AD) is the accumulation of extracellular amyloid-beta protein in cortical regions of the brain. For a definitive diagnosis of AD, post-mortem histological analysis, including sectioning and staining of different brain regions, is required. Here, we present optical coherence tomography (OCT) as a tissue-preserving imaging modality for the visualization of amyloid-beta plaques and compare their contrast in intensity- and polarization-sensitive (PS) OCT. Human brain samples of eleven patients diagnosed with AD were imaged. Three-dimensional PS-OCT datasets were acquired and plaques were manually segmented in 500 intensity and retardation cross-sections per patient using the freely available ITK-SNAP software. The image contrast of plaques was quantified. Histological staining of tissue sections from the same specimens was performed to compare OCT findings against the gold standard. Furthermore, the distribution of plaques was evaluated for intensity-based OCT, PS-OCT and the corresponding histological amyloid-beta staining. Only 5% of plaques were visible in both intensity and retardation segmentations, suggesting that different types of plaques may be visualized by the two OCT contrast channels. Our results indicate that multicontrast OCT imaging might be a promising approach for a tissue-preserving visualization of amyloid-beta plaques in AD.

Retinal analysis of a mouse model of Alzheimer’s disease with multicontrast optical coherence tomography

“…It has also been previously concluded that not all plaques are visible by either contrast modality. 60 Hence negative OCT findings do not rule out the presence of retinal Aβ plaques. Even if plaques could be seen in the retina with OCT, it would be difficult to distinguish them from the HRF and the depolarizing deposits which are already present in these retinas as observed in Fig.…”

Ex-vivo Alzheimer’s disease brain tissue investigation: a multiscale approach using 1060-nm swept source optical coherence tomography for a direct correlation to histology

“…As described by Gesperger et al, multiple single plaques in the immediate vicinity detected by histology might also be mistaken for a single, large plaque due to the limited resolution of our OCT setup. 23 Therefore, our OCT setup might not be capable of visualizing all amyloid plaques. Further, the contrast in OCT images depends on the detected scattering signal, which in the case of the amyloid-beta plaques depends on the shape, size, and composition of these structures.…”

“…18 A polarization sensitive (PS)-OCM setup at 840 nm was later utilized to identify plaques in postmortem brain tissue based on their intrinsic birefringence. 19 Recently, Gesperger et al 23 conducted a study using a commercial PS-OCT setup to categorize A-β plaques depending on their inherent intensity and PS signal. Using visible light OCT, A-β plaques in murine and human brain tissue down to a diameter of 10 μm were visualized.…”

“…In OCT images, the contrast is based on the inherent hyperscattering properties of these plaques. 18 – 23 First, in 2012, plaques were investigated using a Bessel beam illumination OCM setup operating at 800 nm. 18 A polarization sensitive (PS)-OCM setup at 840 nm was later utilized to identify plaques in postmortem brain tissue based on their intrinsic birefringence.…”

“… 19 Recently, Gesperger et al. 23 conducted a study using a commercial PS-OCT setup to categorize plaques depending on their inherent intensity and PS signal. Using visible light OCT, plaques in murine and human brain tissue down to a diameter of were visualized.…”