PROJECT SUMMARY / ABSTRACT Coronary artery disease, aggravated by arterial calcification, poses a significant challenge to successful percutaneous coronary intervention (PCI). Coronary artery calcification (CAC) reduces vessel compliance and increases the complexities of stent deployment, stent expansion, balloon expansion, and results in uneven drug distribution. Specifically, reduced vessel compliance prohibits stent delivery and reduces the ability of deployed stents to expand, or causing “stent regret”, resulting in stent failure through either restenosis or stent thrombosis. Importantly, these complications are exasperated in highly stenotic CAC lesions – hence, endovascular devices and therapeutic techniques are needed with improved safety and efficacy to advance the clinical management of CAC. The objective of this proposal is to develop novel metasurface optical guidewires for therapeutic applications to treat previously untreatable highly stenotic CAC lesions. Our project addresses these challenges by hypothesizing that: 1) metasurfaces are specialized planar lens elements that can provide optimal energy delivery over a sub-millimeter profile; 2) with advances in fiber-coupled diode laser technologies, fiber-optic metasurfaces are an attractive platform for endovascular devices; 2) a flexible, small-diameter fiber-optic embedded guidewire with metasurfaces – termed 'metasurface optical guidewires' – can offer dual benefits of a rapid exchange monorail for PCI devices and provide light-based endovascular therapeutic capabilities including laser intravascular lithotripsy (L-IVL). The metasurface optical guidewires and associated innovative light-based endovascular therapies will be successfully developed and demonstrated by completing the following specific aims: Aim 1: Design, develop and manufacture metasurface optical guidewires for precise control of intravascular laser dosimetry; Aim 2: Develop a PCI workflow for use of an metasurface optical guidewire for laser intravascular lithotripsy (L-IVL); Aim 3: Develop a PCI workflow and study L-IVL’s efficacy in a preclinical model; Aim 4: Evaluate L-IVL treatment efficacy in a pre-clinical CAC animal model. Successful completion of these aims will lead to the development of the metasurface optical guidewire and other innovative devices and procedures that can significantly improve PCI outcomes in patients with calcified coronary arteries, reducing complications and enhancing patient care.