Depth-Resolved Assessment of Atherosclerosis by Intravascular Photoacoustic-Ultrasound Imaging

Coronary heart disease is the leading cause of death in the United States and the incidence is projected to increase by 18% by 2030. Yet, there remains a pressing clinical need for tools to detect vulnerable atherosclerotic plaques that can rupture and lead to major adverse cardiac events. Plaques that are considered most vulnerable for rupture are thin-capped fibroatheromas, which are grossly defined by hallmarks of a thin fibrous cap, a large lipid-rich necrotic core, inflammatory infiltrate, and positive remodeling. These plaques are often structurally non-obstructive to moderately obstructive, thus asymptomatic and clinically unidentifiable with routine angiography and stress testing. Rather, their vulnerability is a product of their chemical composition. We have developed a dual-mode intravascular catheter which is capable of producing co-registered cross-sectional images of arterial wall morphology and lipid content, via ultrasound and photoacoustic modes, respectively. Validation of this capability will rely on interrogation of atherosclerotic coronary arteries from humans and peripheral arteries from swine, with comparison to gold-standard histopathology and competing technologies. Here, we present ex vivo validation of a novel intravascular photoacoustic-ultrasound (IVPA-US) imaging catheter and the first systematic in vivo IVPA-US imaging study in a preclinical swine model with native disease, necessary benchmarks before proceeding with translation to clinic. We aim to ultimately demonstrate predictive utility to detect plaques that are vulnerable to rupture and trigger adverse cardiac events. In addition, this will be instrumental in elucidating the mechanism of plaque rupture, the development of preventive and therapeutic interventions, and reducing coronary heart disease-related mortality

Optical coherence tomography for the assessment of coronary atherosclerosis and vessel response after stent implantation

Optical Coherence Tomography (OCT) is a light-based imaging modality that can provide in vivo high-resolution images of the coronary artery with a level of resolution (axial 10-20 µm) ten times higher than intravascular ultrasound. The technique, uses low-coherent near infrarred light to create high-resolution cross sectional images of the vessel. The technology refinement achieved in the last years has made this imaging modality less procedurally demanding opening its possibilities for clinical use. The present thesis provides im

Progress in atherosclerotic plaque imaging

Cardiovascular diseases are the primary cause of mortality in the industrialized world, and arterial obstruction, triggered by rupture-prone atherosclerotic plaques, lead to myocardial infarction and cerebral stroke. Vulnerable plaques do not necessarily occur with flow-limiting stenosis, thus conventional luminographic assessment of the pathology fails to identify unstable lesions. In this review we discuss the currently available imaging modalities used to investigate morphological features and biological characteristics of the atherosclerotic plaque. The different imaging modalities such as ultrasound, magnetic resonance imaging, computed tomography, nuclear imaging and their intravascular applications are illustrated, highlighting their specific diagnostic potential. Clinically available and upcoming methodologies are also reviewed along with the related challenges in their clinical translation, concerning the specific invasiveness, accuracy and cost-effectiveness of these methods

Intravascular photoacoustics as a theranostic platform for atherosclerosis

textThe persistence of high global mortality rates directly attributable to cardiovascular disease drives ongoing research into novel approaches for improved diagnosis and treatment of its primary underlying cause, atherosclerosis. Combined intravascular ultrasound and photoacoustic (IVUS/IVPA) imaging is one such modality, actively being developed as a tool for improved characterization of high-risk atherosclerotic plaques. The pathophysiology associated with progression and destabilization of atherosclerotic plaques leads to characteristic changes in arterial morphology and composition. IVUS/IVPA imaging seeks to expand upon the ability of clinically utilized intravascular ultrasound (IVUS) imaging to assess vessel anatomy by adding improved sensitivity to image the underlying cellular and molecular composition through intravascular photoacoustic (IVPA) imaging of either endogenous chromophores (e.g. lipid) or exogenously delivered contrast agents. This dissertation focuses on the expansion of IVUS/IVPA imaging using exogenous contrast agents to enable the detection and subsequent optically-triggered therapy of atherosclerotic plaques. The passive extravasation and aggregation of systemically injected plasmonic gold nanorods absorbing within the near infrared tissue optical window within plaques of atherosclerotic rabbit models is first demonstrated, along with the ability to localize the contrast agents using ex vivo IVUS/IVPA imaging. The motivation for nanoparticle labeling of atherosclerosis is then expanded from that of purely image contrast agents to vehicles for image-guided, dual-modality phototherapy. The integrated IVUS/IVPA imaging catheter is utilized for photothermal delivery with simultaneous IVPA temperature monitoring using the high optical absorption of gold nanorod contrast agents to enable localized heating. Subsequently, the potential role for IVUS/IVPA-guided phototherapy is further expanded through the characterization and in vitro assessment of novel multifunctional theranostic nanoparticles comprised of a gold nanorod core with a degradable, photosensitizer-doped silica shell. Together, the results presented within this dissertation provide a framework for ongoing research into the expansion of IVUS/IVPA imaging as a platform for complimentary diagnosis and local treatment of atherosclerotic plaques using multifunctional theranostic nanoparticle contrast agents.Biomedical Engineerin

Advances in IVUS/OCT and Future Clinical Perspective of Novel Hybrid Catheter System in Coronary Imaging

Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed and improved as both diagnostic and guidance tools for interventional procedures over the past three decades. IVUS has a resolution of 100µm with a high tissue penetration and capability of assessing the entire structure of a coronary artery including the external elastic membrane, whereas OCT has a higher resolution of 10–20µm to assess endoluminal structures with a limited tissue penetration compared to IVUS. Recently, two companies, CONAVI and TERUMO, integrated IVUS and OCT into a single catheter system. With their inherent strength and limitations, the combined IVUS and OCT probes are complementary and work synergistically to enable a comprehensive depiction of coronary artery. In this review, we summarize the performance of the two intracoronary imaging modalit

Focus on the research utility of intravascular ultrasound - comparison with other invasive modalities

Intravascular ultrasound (IVUS) is an invasive modality which provides cross-sectional images of a coronary artery. In these images both the lumen and outer vessel wall can be identified and accurate estimations of their dimensions and of the plaque burden can be obtained. In addition, further processing of the IVUS backscatter signal helps in the characterization of the type of the plaque and thus it has been used to study the natural history of the atherosclerotic evolution. On the other hand its indigenous limitations do not allow IVUS to assess accurately stent struts coverage, existence of thrombus or exact site of plaque rupture and to identify some of the features associated with increased plaque vulnerability. In order this information to be obtained, other modalities such as optical coherence tomography, angioscopy, near infrared spectroscopy and intravascular magnetic resonance imaging have either been utilized or are under evaluation. The aim of this review article is to present the current utilities of IVUS in research and to discuss its advantages and disadvantages over the other imaging techniques

Multimodality Imaging to Detect Vulnerable Plaque in Coronary Arteries and Its Clinical Application

Postmortem studies have described the association between the thin-cap fibroatheroma (TCFA) and the occurrence of acute coronary syndrome (ACS). Both noninvasive and invasive techniques have been refined and used as a research tool to visualize the plaque at a high risk of disruption. There has been a considerable effort to develop the imaging modalities that offer detailed visualization of coronary pathology and accurately predict the adverse cardiac outcomes. This chapter provides an overview of the current and experimental coronary imaging methods to detect vulnerable plaque and discuss the potential implication of multimodality imaging in clinical practice