Optical coherence tomography for the evaluation of vulnerable plaques with nanoprobes

This project aims to design and develop a robust diagnostic intravascular imaging system for in situ detection of labeled coronary vulnerable plaques, consisting in the integration of targeted nano-probes with a novel protocol for IV-OCT (Intravascular optical coherence tomography) imaging, to analyze anatomical and molecular features of plaques with high precision, sensitivity and specificity. This approach to molecular imaging using IV-OCT focuses primarily in the investigation of possible contrast agents. Thus, this study is composed, in addition to their functionalization, by the comparison of gold nanostars and Poly(n-butyl cyanoacrylate) (PBCA) microbubbles as possible candidates. The results show a special attention to PBCA microbbubles being that they exhibited the most noticeable scattering e↵ect leading to more valuable imaging. A three-dimensional structured tissue-mimicking phantom was also presented for use in IV-OCT. The phantom was fabricated from a PDMS matrix and titanium dioxide additive, capable of producing a wide variety of scattering densities. We describe the fabrication, characterization and IV-OCT imaging of these phantoms and demonstrate their utility in functionalization with two types of contrast agents. Finally, commercial Endothelium-targeted PBCA microbubbles (Fujifilm Visualsonics) were tested using clinical IV-OCT systems in post mortem human arteries allowing its unequivocal location in the sample. The results present the first steps towards adding to the routinely used IV-OCT a new functionality. Dissertation goals: Contrast agent-aided molecular imaging process. The direct visualization of endogenous disease markers in the body is nonexistent as it is not possible to distinguish from surrounding tissue using OCT imaging. The proposed method rests in the use of exogenous contrast agents with the specificity to bind to the target in question. Image designed in Adobe Illustrator®