Pathological aging of the brain can be linked to neurodegenerative diseases such as Alzheimer’s and Parkinson’s, cerebrovascular diseases or less common conditions such as NPH. NPH is a form of neurodegenerative disease associated with disorders of cerebrospinal fluid (CSF) circulation, usually diagnosed through a combination of clinical evaluation, brain imaging, and assessment of the ICP response to controlled perturbation to the cerebrospinal system induced by constant rate infusion of fluid. NPH is one of the few neurodegenerative diseases that can potentially be treated by ventricular shunting. Nevertheless, the pathophysiology of the disease, including its relationship with system factors and the precise characterization of the patients’ ICP profiles, is still under investigation. In recent years, the focus in ICP analysis has shifted from the traditionally analyzed time-averaged values towards analysis of short-term oscillations related to the cardiac cycle. The shape of these oscillations, known as ICP PW morphology, is associated with the state of the cerebrospinal system’s ability to buffer changes in intracranial volume, but their precise origin and dependence on other factors such as age or the function of the autonomic nervous system remain mostly unknown. The aim of this project is to merge medical, physical and biomedical engineering approaches to better understand the mechanical and biological factors that determine the shape of ICP PW in NPH patients, and therefore allow for more accurate diagnosis and treatment of patients suspected of the disease.

It is within that context that we propose a joint research project between Sante Ingenierie Biologie a Saint-Etienne (SAINBIOSE) unit of the French National Institute of Health and Medical Research (INSERM) in Saint-Etienne, France and Neuroengineering Laboratory (BrainLab) located in Wroclaw, Poland, with support from the Toulouse NeuroImaging Center (TONIC) unit of INSERM, the University Hospital of Toulouse, and the Toulouse Institute of Fluid Mechanics (IMFT). Through the proposed personnel exchange we plan to merge two branches of studies on the physiology and pathophysiology of cerebrospinal fluid circulation represented by those institutions: biomechanical modeling combined with brain imaging and proteomic analysis and biomedical signal processing and artificial intelligence approaches to analyzing ICP PW. The project will encompass three major research tasks: identification of the mechanical determinants of ICP PW shape, investigation of biological contributors to ICP PW shape, and assessment of the impact of altered hemodynamic regulatory system on the ICP PW shape.