There is a pressing need for techniques with enough sensitivity to detect early signs of neurodegeneration and define biomarkers of neurodegenerative diseases. The recent failure of clinical trials on Alzheimer’s disease shows that it is very difficult to have successful therapies in the late stages of the disease, which are characterized by massive neuronal loss. This justifies the importance of detecting neurodegenerative diseases in their asymptomatic phase.
The traditional modalities of brain imaging, Magnetic Resonance Imaging (MRI) and Computerized Tomography, rely on volumetric changes and lack sensitivity for detecting the subtle alterations that precede clinical symptoms. As the mechanical properties of soft tissue vary over a much greater range than other physical properties, elastography techniques are inherently very sensitive. Magnetic Resonance Elastography (MRE), an imaging modality that measures the stiffness of tissues by imaging through MRI the displacements induced by mechanical waves, demonstrated that inflammation, toxic demyelination and transitory ischemic damage affect directly the brain mechanical properties. These findings support the idea that imaging the mechanical properties can detect changes in the brain's microstructure before volumetric changes or neuronal losses become detectable.
Although MRE offers the prospect of detecting neurodegeneration in its asymptomatic phase, its use as a biomarker will always be hampered by its high-cost making impracticable its application to longitudinal studies or for screening populations. For these purposes, low-cost and easy access are mandatory.
The retina is the visible part of the central nervous system and has been explored for signs of neurodegeneration. Our previous research showed that it is possible to develop neurodegeneration biomarkers based on data from Optical Coherence Tomography (OCT) images of retinas without any visible structural alteration. These results came from Alzheimer's, multiple sclerosis and Parkinson's patients. More recently, we obtained biomarkers for Alzheimer's disease (AD) using data from OCT in vivo images of the retina of the triple-transgenic mouse model of AD (3xTg-AD).
From the rationale of brain MRE and our results on OCT neurodegeneration biomarkers, we believe that it is possible to detect early signs of degeneration by measuring the mechanical properties of the retina with an OCT-based elastography technique. Since OCT is a relatively low cost, easy to operate, widespread imaging technique, it has the conditions to be used for screening purposes.
Therefore, in this project we propose to develop an Optical Coherence Elastography technique for imaging in vivo the mechanical properties of the retina of animal models. The technique will combine ultrasound excitation with OCT imaging. The instrumentation will be based on an existing Swept-Source OCT system, entirely developed by us, ensuring full control over data acquisition and processing.
Project funded by Portuguese funds through /MCTES and co-funded by the European Regional Development Fund (FEDER) through the Operational Thematic Program for Competitiveness and Internationalization (POCI), COMPETE 2020."
ADDF - Association for the development of the Department of Physics
LIBPhys-UC (Laboratory for Instrumentation, Biomedical Engineering and Radiation Physics)
Reference: PTDC/EMD-EMD/32162/2017 (POCI-01-0145-FEDER-032162)
Start: 1st of October, 2018
End: 30st of September, 2021
Budget: 239 702 €