OPTIMALZ - Optical imaging of ocular pathology in Alzheimer’s disease

Website: ERC Website

Novel diagnostic techniques and disease models have the powerful potential to provide new insights into pathological and pathophysiological processes. Ocular manifestations of Alzheimer’s disease (AD) emerge as novel and attractive alternative to investigate disease progression in parallel to the brain. Using the eye as a window to the brain, we propose to develop multi-functional optical coherence tomography (OCT) as a noninvasive in-vivo technique for preclinical imaging of AD pathology. OCT is analogous to ultrasound B-mode imaging, using light rather than acoustical waves, and performs high-resolution real time 3D imaging of microstructure in biological tissues in situ. Based on the optical polarization properties or movement of particles, functional OCT methods provide additional contrast channels. In the proposed project, we will unite/join standard and functional OCT for imaging ocular and cerebral pathology in AD mouse models with threefold contrast. Structural changes caused by neuronal cell loss in the retina will be assessed longitudinally and with micron-scale resolution. Beta-amyloid plaques are birefringent and are deposited in both brain and retina in AD. We propose to exploit these intrinsic polarization properties for noninvasive detection and longitudinal characterization/assessment of retinal plaque load. Simultaneously, we will assess AD-related changes in retinal microvasculature. Retinal blood flow will be measured in quantitative units and monitored during disease progression. In addition to the retina, we will perform longitudinal imaging of AD-related lesions in the ocular lens with OCT. By correlating ocular AD pathology as imaged with OCT to cerebral lesions, the proposed research provides a new set of in vivo parameters that potentially shed new light on the pathogenesis and impact early diagnosis of AD in aging populations worldwide.

Preclinical imaging of the rodent eye with multi-functional optical coherence tomography

Website: https://pf.fwf.ac.at/en/research-in-practice/project-finder/30037

Major causes of blindness are still not entirely understood which complicates early diagnosis and hinders the development of proper treatment. In order to understand the pathogenesis of vision threatening diseases such as age-related macular degeneration (AMD) or glaucoma, a variety of small animal models have been developed. The gold standard for such preclinical investigations is histology which provides microscopic images of anatomic details and tissue microstructure. However, animals have to be killed in order to perform histology. Hence, there is a great demand for non-invasive imaging methods in order to enable the measurement of anatomical and physiological parameters in vivo and in situ, to reduce the number of animals required, and to enable longitudinal studies in the same animal.

It is the aim of this project to develop multi-functional optical coherence tomography (OCT) as a non-invasive alternative to histology in preclinical research in rodent models. OCT is an emerging optical technology which performs high-resolution, cross-sectional and three-dimensional (3D) imaging of tissue morphology in situ and in real time. OCT has become a clinical standard in human ophthalmology and was recently demonstrated as a feasible tool for imaging the rodent retina. Functional OCT methods such as polarization sensitive (PS) OCT and Doppler OCT provide additional information about tissue structure (polarization properties) and function (blood flow) that is inaccessible with standard OCT technology images based solely on the intensity of backscattered light. The additional contrast provided by functional OCT methods extends and improves image contrast and enables quantitative measurements.

In this project, a novel multi-functional OCT system will be developed and optimized for both PS- and Doppler OCT imaging in a single system in the mouse and rat eye. Using this system, the following properties and parameters of healthy rodent eyes will be investigated in order to set the base for investigations in disease models:

-Quantitative mapping of melanin pigmentation based on depolarization of light
-Measurement of retinal nerve fiber layer birefringence
-Measurement of scleral fiber orientation and birefringence
-Mapping retinal vasculature and blood flow measurement

For validation, the results will be correlated with state-of-the-art confocal, two photon and electron microscopy of histological sections of the same structures. Finally, relevant rodent models in AMD and glaucoma research will be investigated with the multi-functional OCT system in order to study the pathogeneses and to identify early disease markers. Quantitative functional imaging will provide access to a set of anatomical and physiological parameters that cannot be accessed using any other previously reported techniques. Furthermore, since future biomedical research based on OCT supports the principle of the "Three R's," to Replace, Reduce and Refine the use of animals for scientific purposes.