1. Development of integrated OCT/US/PAT system for intravascular Imaging
Coronary artery disease (CAD) is the most prevalent cardiovascular disease, impacting over 18 million adults and causing more than 350,000 deaths annually in recent years. Acute coronary events are primarily caused by ruptured atherosclerotic plaques, emphasizing the need for early detection and accurate identification of plaque types (stable versus vulnerable) as the first line of defense. Obtaining detailed morphology and functional information on atherosclerotic plaques is crucial for advancing clinical management of atherosclerosis. The objective of this proposal is to develop a single intravascular imaging system incorporating intravascular ultrasound (IVUS), photoacoustic tomography (PAT), optical coherence tomography (OCT), and polarization-sensitive OCT (PSOCT) to study and characterize plaque vulnerability. The multimodal imaging probe, requiring only a single disposable guide wire and catheter, aims to reduce costs, risks, procedure time, and radiation exposure. Building upon integrated IVUS/OCT and IVUS/PAT technology developed in our lab, the proposed OCT/US/PAT system includes significant advancements for enhanced clinical translation. It combines the high molecular sensitivity of PAT at 1720 nm, broad imaging depth of US, high spatial resolution, and extended penetration depth of 1.7-μm OCT, along with mechanical evaluation using PSOCT. The system provides physicians with a powerful clinical instrument for studying, diagnosing, and managing vulnerable plaques. The specific aims are to: 1) Design and construct a multimodal confocal OCT/US/PAT imaging probe; 2) Design and develop the OCT/US/PAT system using a 10-kHz, 1720 nm pulsed laser for PAT and a 100-kHz swept-source laser for OCT/PSOCT; 3) Demonstrate the efficacy of the proposed system via in vivo porcine model. We expect the development of the proposed OCT/US/PAT technology to bring tremendous impact to both basic science and clinical understanding of plaque pathogenesis. This will enhance the clinicians’ ability to identify vulnerable lesions, tailor interventional therapy, and monitor disease progression. More importantly, it will be a powerful tool that provides a quantitative means to benchmark and evaluate new medical devices and therapies.
2. In vivo lmaging and Quantification of Cilia Beating Dynamics Using Phase-Resolved Optical Imaging Technology
Each year, 50M Americans suffer from chronic rhinosinusitis (CRS) and allergic rhinitis (AR). The economic impact accounts for over $35B/year in health care expenditures alone, with over 3.5M work and 2M school days lost each year. Accordingly, over 600K operations per year are performed to treat sinonasal disease. The disease burden is immense with a profound reduction in quality of life, and is often overlooked because mortality is low, while morbidity is high. Currently, patient-reported outcome measures are used to evaluate disease status in CRS and AR, as there are no reliable quantitative methods to gauge disease severity or response to therapy. Success or failure is determined by the subjective reports from the patient alone, or via physician-directed endoscopy, where interpretation may also be subjective. One potential biophysical variable that can be measured is ciliary beat frequency (CBF). The cilia control mucociliary transport, which is the endpoint physiologic function of the sinonasal mucosa. CBF is challenging to measure in vivo in a clinical setting, but has value in potentially monitoring mucosal health and the response to therapy. This proposal is in response to the PAR-19-158 NIBIB Bioengineering Research Grants and aimed to develop and validate an innovative in vivo imaging system to measure CBF and the related physiological parameters that characterize mucosal health. Drs. Chen and Wong have had continuous collaborations for over 20 years with expertise in optical imaging, system, and probe designs, as well as translating these bench-top technologies to clinical applications. This proposal centers on the design, construction, and clinical evaluation of phase-resolved spectrally encoded endoscopy (PR-SEE) integrated with optical coherence tomography (OCT). PR-SEE will enable functional imaging of the nasal mucosa in vivo, allowing surveying the CBF landscape across the nasal mucosa as well as facilitating the analysis of ciliary beat pattern (CBP). More importantly, PR-SEE will provide a rigorous means to assess the speed, amplitude, and propagation of the mucosal metachronal waves (MWs), which are the quantifiable endpoint function of mucociliary transport. The proposed imaging device concentrates on a coaxial scanning scheme encompassing spectrally encoded interferometry and OCT to overcome the current limitations for in vivo cilia imaging. To evaluate and validate our device, we will first perform PR-SEE on a rabbit nasal airway model, followed by imaging of anesthetized patients in the operation room to obtain ciliary functional parameters (CBF, CBP, MWs). Sixty subjects undergoing nasal operations (normal control, e.g., septoplasty) or sinus surgeries (CRS patients) will be recruited for the study. Successful clinical translation in the operation room will prepare PR-SEE for imaging awake patients in the office in subsequent studies. We firmly believe that enabling functional quantification of mucosal health will jumpstart the developments in pharmacotherapy, devices, and surgical intervention.
3. Phase resolved ARF optical coherence elastography for intravascular imaging
Cardiovascular disease is responsible for 1 in 4 deaths, or 650,000 Americans, every year. It is the leading cause of death in the United States. Ruptured atherosclerotic plaques are the main cause of acute coronary events, and it is of lethal consequence. Clinically, early detection of the latent vulnerability of plaques is the first line of defense against such deadly circumstances, and it relies on visualizing both tissue structural and biomechanical properties. Accurate characterization of a plaque lesion can facilitate better treatment management by further our understanding in the disease progression. The long-term objective of this proposal is to develop a multimodal intravascular imaging system that combines optical coherence tomography (OCT), ultrasound imaging (US), and shear-wave-based optical coherence elastography (OCESW) for studying and characterizing plaque vulnerability. The proposed system, IVOCT-US-OCESW, is built upon the ARF-OCE technology developed in the preceding proposal, with several significant technical advancements that will further facilitate its clinical translation. The proposed IVOCT-US- OCESW system unifies the high spatial resolution and extended penetration depth of the 1.7-µm OCT, the broad imaging depth of US, and the enhanced biomechanical contrast of OCESW. It will provide physicians a powerful clinical instrument for studying, diagnosing, and managing vulnerable plaques. The multimodal probe only requires a single disposable guide wire and catheter, thereby reducing the costs, procedure length, associated risks, and X-ray exposure. Our specific aims are to: 1) Design and construct a multimodal IVOCT-US-OCESW imaging probe; 2) Develop the IVOCT-US-OCESW system featuring a 4-MHz, 1.7-µm laser; 3) Establish a scanning protocol and algorithms for biomechanical property quantification; 4) Demonstrate the efficacy of the proposed system in normal and diseased animal models. We expect the development of the proposed high-speed, high-penetration-depth, and high-sensitivity IVOCT-US-OCESW system and probe to have significant impact to both basic science and clinical understanding of plaque pathogenesis. This will enhance the clinicians’ ability to identify vulnerable lesions, tailor interventional therapy, and monitor disease progression. More importantly, it will be a powerful tool that provides a quantitative means to benchmark and evaluate new medical devices and therapies.
