Measuring small vessel functional alterations with ultrasound – PERI-fUS

Early small-sized blood vessel dysfunctions are increasingly recognized to contribute to the initial stages of many neurodegenerative diseases such as Alzheier's disease or vasculara dementia, long before cognitive impairments appear and conventional markers (Amyloid ß, P-tau). These include Alzheimer’s disease (AD) and vascular dementia that account for 90% of cases. They are a leading cause of death and disability with as far, no treatment with validated efficacy to prevent or delay brain damage. The development of drugs targeting vascular dysfunctions at its earliest stages could pave the road towards the development of novel therapies for dementia. However, this therapeutic will require the identification of vascular biomarkers of disease progression for early diagnosis as well as for monitoring drug action.
The goal of the perifUS project is to investigate new methodologies to assess the alterations of the neurovascular coupling through the measurement of the hemodynamic response function at the earliest possible stage using non invasive functional ultrasound (fUS).
We will develop robust and non-invasive technologies for the measurements of the neurovascular response in the mouse brain transcranially. Using several genetic mouse models of inherited small cerebral vessel disease (sCVD), we will identify early functional neurovascular markers that could ultimately be translated in clinics to monitor disease progression. Finally, we will develop and evaluate the measurement of the hemodynamic response function in the retina as it could provide a unique window to the brain for early diagnosis and treatment monitoring in clinics.