|
Atherosclerosis, a condition in which plaque accumulates on the inner wall of arteries, is often recognized as a precursor to cardiovascular diseases (CVDs), the most common causes of death in the US. Optical Coherence Tomography (OCT) is an intravascular optical diagnosis tool, which can be used to obtain high resolution morphological images of atherosclerotic plaque. However, atherosclerotic plaque components, such as macrophages, can be misclassified due to their signal similarities to fibrin accumulations, cholesterol crystals and microcalcifications. To overcome these challenges, we develop a biocompatible contrast agent to enhance molecular imaging of a Pump-Probe OCT (PPOCT) system. Methylene blue (MB) was encapsulated into poly lactic-co-glycolic acid (PLGA) particles by an emulsion/solvent evaporation technique. Fabrication parameters were controlled to synthesize particles with desired properties such as: size, encapsulation efficiency, degradation rate, and particle surface functionalization. The encapsulation of MB protects it from the enzymatic reduction to leuco-methylene blue (92.8 % protection), and reduces the singlet oxygen generation by the excited MB molecules by 78.3%. Likewise, the PLGA shells improve the OCT signal by enhancing the scattering of light. The surface of particles was modified with ligands that can target molecular biomarkers involved in atherosclerotic plaque formation such as vascular cell adhesion molecules (VCAM-1) and apoptotic macrophages. This modification is expected to enhance tissue selectivity, provides detailed information on the local biochemistry and yields visualization of pathological processes. PLGA-based contrast agents were tested in human postmortem artery sections to study particles permeability as a function of particle size and its molecular selectivity.
|
