Abstract
Purpose :
The purpose of the current study was to evaluate the potential of multispectral high-resolution imaging to identify amyloid β-protein (Aβ) deposits in the retina as a biomarker for neurodegenerative diseases such as Alzheimer’s (AD). We combined simultaneous multi-channels offset and confocal AO-SLO imaging, which provides isotropic images of retinal microstructures free of directionality artifacts, with spectral signature analysis of chemical compounds to identify such biomarkers at cellular-level.
Methods :
We have developed a multispectral imaging technique for identifying chemical compounds in vivo in the retina with cellular-level resolution and without the use of contrast agents. Since various retinal structures and cells have different reflectance and absorbance properties, information about cell metabolism and structure can be obtained using spectral imaging. Our method is based on using multiple wavelengths for which Aβ has different attenuation (405 nm, 450 nm, 488 nm, 520 nm and 640 nm). In this way, Aβ can be spectrally differentiated from the surrounding tissue. Our instrument is based on PSI high-resolution retinal imaging platform (MAORI for human and MAOSI for rodent imaging) which has multi-offset capabilities. However, similar to all current AO-SLO systems, our instruments use a single broadband light source (20-50 nm bandwidth) and detect the reflected light with detectors that integrate over the entire spectrum, without spectral differentiation capabilities. To add multispectral capabilities, we replaced the SLO light source with a time-wavelength multiplexed light source to which we synchronized the detection unit.
Results :
One confocal and four offset images are acquired for each individual illumination wavelength. Multiple split, phase, phase gradient, sum (ring detection), and standard deviation images are derived for each color and are combined in a manner that highlights spectrally the local variations of attenuation through spectral similarity analysis. The new concept has been demonstrated in a model eye using commercially available Aβ and in vivo on a mouse Alzheimer’s model.
Conclusions :
PSI has developed a novel multispectral adaptive optics-based technique for non-invasive detection at cellular-level of Aβ in the retina. This technique may pave a path forward for better understanding of the onset of various neurodegenerative diseases.
This abstract was presented at the 2024 ARVO Imaging in the Eye Conference, held in Seattle, WA, May 4, 2024.