Positron Annihilation Lifetime Spectroscopy for Revealing and Quantifying Inflammation and Endothelial Diseases

forthcoming

Inflammatory processes have been identified as major contributors to various mental and physical diseases, significantly impacting global morbidity and mortality. Many of these conditions involve changes in the microvascular permeability that are challenging to early detect due to limitations in current diagnostic tools, which are either invasive or lack sufficient resolution. There is an urgent need for improved methods to detect and measure microvascular permeability. To advance the field, I will use Positron Annihilation Spectroscopy (PAS) to quantify alterations in the capillary endothelial wall integrity directly, known to be correlated to the endothelial permeability. PAS is a non-destructive, label-free technique that measures molecular dynamics at the nanoscale. By irradiating materials with positrons and analyzing their resulting annihilation events, PAS can provide real-time observations of nanostructural changes in biological tissue. To achieve my goal, I will engineer a robust capillary endothelial wall model and I will characterize endothelial wall permeability changes under various pharmacological conditions, by using electrophysiological techniques. To perform intravital PAS on this in vitro model, I will develop a novel perfusion bioreactor, able to withstand high vacuum conditions and to interface biological matter with positron sources. I will then correlate PAS outputs with the ones of conventional techniques. To optimize drug concentration required to measure PAS variations, I will realize a numerical predictive model. Finally, I will validate my approach on the highly vascularized respiratory membrane of embryonated avian eggs. This project combines bioengineering, particle physics, and medical imaging to address a critical gap in current diagnostic capabilities, revolutionizing preventive diagnostics, and offering patients a new tool for early detection of inflammatory and endothelial diseases, that could improve their life expectancy.