Elastografia de coerência óptica da retina in vivo para detecção precoce de neurodegeneração

This project aims to test if Optical Coherence Elastography (OCE) can detect in vivo subtle changes in the mechanical properties of the retina, during the asymptomatic phase of Alzheimer's Disease, supporting the development of a biomarker for early detection of this disease. To answer this research question, we will (1) develop a multi-layered numerical model representing the retina's viscoelasticity, for obtaining the viscoelastic properties of the retina from the displacements’ maps measured by OCE; (2) develop image processing algorithms for correcting the effect of motions not related with the mechanical excitation of the retina; and (3) conduct an animal study comparing wild-type (control) mice and the triple-transgenic mouse model of Alzheimer’s Disease (AD), using our OCE system, developed during a previous project. We will also evaluate the feasibility of using the oculocardiac pulse as the mechanical excitation source in passive retinal OCE. The long-term goal is to detect AD in its asymptomatic stage and support the development of a biomarker for early detection of this disease. Early detection of AD is of extreme importance. The huge failure rate of AD drug trials shows that it is very difficult to have successful therapies in the late stages of the disease, characterized by massive neuronal loss. This justifies the importance of developing techniques with enough sensitivity to detect neurodegenerative disorders in their asymptomatic phase, which extends for 10–20 years before clinical manifestations. Fulfilling this major goal requires a distinct approach from currently applied techniques. Traditional brain imaging modalities rely on volumetric changes and lack sensitivity for detecting neurodegeneration in the preclinical stage. Magnetic Resonance Elastography (MRE) may overcome this limitation, but its high cost and limited availability hamper its application as a screening tool or a widely applicable diagnostic tool. Instead of imaging directly the brain, we propose to image the retina with non-invasive optical techniques and use it as a window to the brain. Our innovative idea is to look for early signs of neurodegeneration using OCE, an imaging technique based on Optical Coherence Tomography (OCT), a diagnostic method with widespread clinical use in ophthalmology. This idea is supported by the published literature on brain MRE and by our own results on using texture analysis of retinal OCT’s data for detecting neurodegeneration. The project is very challenging. We are dealing with producing a mechanical stimulus and measuring nanometric displacements on a delicate tissue, with complex mechanical properties, constantly experiencing pulsatile and bulk movements and lying deep in the back of the eye. Estimating the mechanical properties will imply solving an ill-posed inverse problem. Findings of anisotropy and nonlinear stress-strain relationship will require departing from the linear isotropic assumption and developing a more complex model for the retina’s viscoelasticity. The method we propose for early AD detection is highly original and goes clearly beyond the state-of-the-art of neurodegeneration detection methods. Innovative contributions will also occur in solving the direct and inverse problems, particularly in the use of neural networks.