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Optical imaging of ocular pathology in Alzheimer’s disease

Periodic Reporting for period 3 - OPTIMALZ (Optical imaging of ocular pathology in Alzheimer’s disease)

Reporting period: 2018-09-01 to 2020-02-29

The research funded by ERC Starting Grant OPTIMALZ (contract number 640396) is focusing on the development and application of novel optical techniques for imaging pathology related to Alzheimer’s disease in the eye and brain. Alzheimer’s disease is the most common form of dementia which affects increasing numbers of patients in our continuously aging society. Therefore, the search for powerful therapeutics as well as for reliable and early diagnostics poses an important research topic for the scientific community. Regarding the eye as an easily accessible outpost of the brain, OPTIMALZ explores new imaging techniques which shine a laser beam onto the neural tissue in the back of the eye and reconstruct 3D images of the optical properties of these tissues. These 3D images can then be investigated in order to spot lesions in the eye related to Alzheimer’s disease. In parallel to the investigating the retina in the back of the eye, we are developing two optical imagers for studying the lens of the eye and brain tissue. Our multidisciplinary team consisting of physicists, engineers, biologists, and neuropathologists will then apply the three prototypes for longitudinal studies of pathological lesions related to Alzheimer’s disease.
Three imaging devices have been developed during the first 3 years of OPTIMALZ. Tailored for imaging retina, lens and brain tissue, the three prototypes are now being tested in longitudinal preclinical studies. Prototype 1 was designed for retinal imaging. Surpassing the resolution of state-of-the-art devices by more than five times, the prototype enables 3D imaging of the retina with sub-micrometer resolution. In addition, it provides enhanced tissue contrast by means of a polarization-sensitive layout such that different retinal structures can be distinguished based on their light polarizing properties. This is particularly interesting for Alzheimer’s disease since we could demonstrate earlier this year that plaques found in the brains of patients can be visualized based on their polarization characteristics. Prototype 2 includes a novel detection unit which can assess the way light is scattered by tissue structures. We experimentally confirmed that this approach can effectively identify lesions in the brain related to Alzheimer’s disease. Prototype 3 is a microscopy setup for three dimensional imaging of tissue samples, thereby providing both ultrahigh resolution and spectroscopic contrast. After having finished the design, assembly, programming, specification measurements and imaging test runs, the diagnostic potential of the three prototypes is now being explored for longitudinal in vivo and ex vivo imaging of Alzheimer’s disease related pathology.
The diagnosis of Alzheimer’s disease is challenging. The advantages of the approach explored in OPTIMALZ are twofold. Firstly, using an optical technique enables rapid, three-dimensional, micrometer-scale resolution imaging at rather low cost. Second, targeting the eye as an easily accessible outpost of the brain, neuropathology may be diagnosed in an unconventional yet simple way. If successful, the methods developed and explored in OPTIMALZ may ultimately open the door to low-cost screening tools of Alzheimer’s disease. Moreover, the technological advances resulting from this project have the potential to impact the development of novel imaging technology in other medical and non-medical fields.
The OPTIMALZ project team in 2017.
Imaging ocular dynamics by high-speed OCT [Augustin SciRep 2017].
Neuritic plaques by polarization-sensitive OCT [Baumann SciRep 2017].
Visible light optical coherence microscope [Lichtenegger BOE 2017].
Ultrahigh-resolution retinal imaging by white light OCT [Harper BOE 2018].