This Project Grant award of $400,000 from the National Science Foundation (NSF) Engineering program (CFDA 47.041) aims to develop a new high-speed 3D dynamic contrast microscopic optical coherence tomography (3D DYC-μOCT) imaging system. The goal is to enable label-free, 3D visualization of ciliary beating dynamics in human airway organoids, which is essential for studying lung diseases and developing improved treatments. The key objectives are to: (1) engineer a broadband, high-coherence...
This Project Grant award of $400,000 from the National Science Foundation (NSF) Engineering program (CFDA 47.041) will fund the development of a new high-speed 3D dynamic contrast microscopic optical coherence tomography (3D DYC-μOCT) imaging system. The goal is to create a label-free optical imaging technology capable of studying ciliary beating dynamics in human airway organoids with high spatial and temporal resolution. This advanced imaging system will provide researchers with a clearer...
This Project Grant award of $674,095, provided by the National Institute of Child Health and Human Development (NICHD) under the Child Health and Human Development Extramural Research program (CFDA 93.865), aims to develop a novel optical imaging technology to directly observe and better understand multiple aspects of mammalian fertilization within the mouse fallopian tube in vivo. The primary products and services to be delivered under this 5-year award include: Integrating expertise in live...
The National Eye Institute (NEI) awarded a $256,296 Project Grant (CFDA 93.867 - Vision Research) to The General Hospital Corporation (Massachusetts General Hospital) to develop new "Auto-Sensing, Instantaneous Adaptive Ranging Optical Coherence Tomography (OCTA)" technology. This technology aims to expand the imaging depth range of OCTA systems, enabling improved visualization of the critical peripheral retinal microvasculature. The project will leverage advances in integrated...
This Project Grant award from the National Eye Institute (NEI) under the Vision Research federal grant program (CFDA 93.867) will fund the development of a new wide-field visible-light optical coherence tomography (WF-VIS-OCT) device to evaluate the oxygen-induced retinopathy (OIR) model in rats. The $623,090 award, effective September 1, 2024, will support the Oregon Health & Science University in three main efforts: 1) developing the WF-VIS-OCT system with 5-mm transverse resolution over a...
This Project Grant award from the National Eye Institute (CFDA 93.867 - Vision Research) to New York University School of Medicine provides $673,747 to develop a visible-to-near-infrared spanning optical coherence tomography (OCT) system capable of imaging retinal structures at a resolution of up to 0.5 microns. The goal is to leverage this advanced OCT technology to study the spatiotemporal relationship of key biomarkers such as macular pigments and retinal pigment epithelium melanosomes, and...
The National Eye Institute (NEI) awarded a $193,168 Project Grant (CFDA 93.867 Vision Research) to Duke University to develop a novel, auto-aligning hand-held optical coherence tomography (OCT) and OCT angiography (OCTA) probe for routine and repeatable high-quality retinal imaging in infants and children. The research aims to address the challenges associated with obtaining consistent OCT and OCTA data capture in uncooperative pediatric patients. The expected outcomes include a set of...
This Project Grant award from the National Cancer Institute (NCI), under the Cancer Detection and Diagnosis Research program (CFDA 93.394), will support the development and clinical validation of an Optical Coherence Tomography (OCT) system and two specialized OCT imaging probes to enhance colorectal cancer screening. The $1,471,777 award to The General Hospital Corporation (doing business as Massachusetts General Hospital) aims to create an OCT system that can obtain 3D microscopic images of...
This Project Grant award from the National Eye Institute (NEI) under the Vision Research program (CFDA 93.867) supports the development of a robotically-aligned optical coherence tomography (RAOCT) system capable of automatically measuring a retinal biomarker, the outer nuclear layer (ONL) thickness, which cannot be reliably identified using standard OCT devices. The $215,454 award to Duke University aims to leverage the micrometer-scale control of the RAOCT system's sample beam to enable...
This federal Project Grant award from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), under the "Discovery and Applied Research for Technological Innovations to Improve Human Health" program (CFDA 93.286), provides $249,000 to Case Western Reserve University to develop an ultrafast photoacoustic histology platform for real-time intraoperative diagnosis. The project aims to create a structured illumination ultraviolet photoacoustic microscopy system capable of...
3D DYNAMIC CONTRAST OPTICAL COHERENCE MICROSCOPY FOR ORGANOID STUDIES - PROJECT SUMMARY OPTICAL COHERENCE TOMOGRAPHY (OCT) IS AN EMERGING BIOMEDICAL IMAGING TECHNOLOGY THAT PROVIDES LABEL-FREE AND DEPTH-RESOLVED IMAGES WITH MICRON-SCALE SPATIAL RESOLUTION AND SUB-MILLISECOND TEMPORAL RESOLUTION. SINCE ITS INCEPTION IN 1991, OCT HAS REVOLUTIONIZED EYE DISEASE DIAGNOSIS WITH OVER 32 MILLION OPHTHALMIC OCT PROCEDURES PERFORMED WORLD-WIDE ANNUALLY. OCT-BASED TECHNOLOGIES HAVE ALSO BEEN EXPONENTIALLY ADOPTED IN A WIDE RANGE OF CLINICAL APPLICATIONS, INCLUDING CARDIOLOGY, ENDOSCOPY, UROLOGY, DERMATOLOGY, AND DENTISTRY. TRADITIONALLY, OCT ONLY PROVIDES TISSUE-LEVEL MORPHOLOGICAL INFORMATION. RECENTLY, THERE IS A SURGE IN EXTENDING THIS LABEL-FREE TECHNOLOGY TO ALSO DELINEATE THE PHYSIOLOGICAL INFORMATION (E.G., CELLULAR VIABILITY, NECROTIC REGIONS, AND GROWTH DYNAMICS) AT THE CELLULAR LEVEL. THE SO-CALLED DYNAMIC CONTRAST MICROSCOPIC OCT (DYC- MOCT) OR DYNAMIC CONTRAST OPTICAL COHERENCE MICROSCOPY (DYC-OCM) IS DISTINGUISHED FROM TRADITIONAL SCATTERING-BASED OCT BY ITS EMPHASIS ON DYNAMIC FLUCTUATIONS: THE MOTIONS OF VIABLE CELLS ARE ACCENTED AGAINST THE MOTIONLESS REGIONS IN THE OCT IMAGES, ENHANCING THE IMAGE CONTRAST AND REVEALING BOTH CELLULAR MORPHOLOGICAL AND PHYSIOLOGICAL INFORMATION. TODAY, THERE ARE TWO DOMINATING DYC-OCM ARCHITECTURES: SPECTRAL-DOMAIN OCM (SD-OCM) AND FULL-FIELD OCM (FF-OCM), EACH OPTIMIZED FOR TEMPORAL ANALYSIS OF DIFFERENT 2D IMAGES. UNFORTUNATELY, NONE OF THE TWO DOMINATING DYC-OCM ARCHITECTURES CAN SUPPORT THE 3D VOLUMETRIC DYNAMIC CONTRAST ANALYSIS EVEN THOUGH ORGANELLES AND CELLS ARE NATURALLY ORGANIZED IN 3D. THIS LIMITATION MAINLY COMES FROM THE FACT THAT BOTH SD-OCM AND FF-OCM CAN ONLY PROVIDE A VOXEL RATE OF ~100 MVOXEL/S BUT A VOXEL RATE EXCEEDING 1 GVOXEL/S IS NECESSARY FOR 3D DYC-OCM. SUCH A HIGH VOXEL RATE HAS EVER ONLY BEEN DEMONSTRATED WITH ANOTHER OCM ARCHITECTURE, SWEPT SOURCE OCM (SS-OCM). EVEN THOUGH SS-OCM CAN BREAK THROUGH THE VOXEL RATE BARRIER, IT SUFFERS FROM POOR AXIAL RESOLUTION, AND THUS ITS ABILITY TO IMAGE CELLULAR STRUCTURE HAS BEEN SEVERELY LIMITED. IN THIS PROGRAM, WE AIM TO DEVELOP THE FIRST 3D DYC-OCM TECHNOLOGY THAT SIMULTANEOUSLY BREAKS THROUGH THE VOXEL RATE AND AXIAL RESOLUTION BARRIERS. WE WILL ACCOMPLISH THE GOAL BY INTRODUCING SEVERAL KEY INNOVATIONS IN PHOTONIC INTEGRATED CIRCUIT TECHNOLOGY TO DEVELOP A NOVEL SWEPT SOURCE ARCHITECTURE (AIM 1) AND A SCALABLE PARALLEL IMAGING PLATFORM (AIM 2). A DUAL-MODALITY IMAGING SYSTEM CONSISTING OF A WIDEFIELD FLUORESCENCE MICROSCOPE AND THE 3D DYC-OCM WILL BE DEVELOPED (AIM 3). VALIDATION EXPERIMENTS WILL BE CONDUCTED USING IN VITRO 3D HUMAN HEART AND INTESTINAL ORGANOIDS (HHO AND HIO, AIM 4). GIVEN THE NON-INVASIVE NATURE OF 3D DYC- OCM, TOGETHER WITH ITS HIGH PENETRATION AND RESOLUTION, WE EXPECT TO OBTAIN A HOST OF NEW INFORMATION ON THE DYNAMICS OF HHO AND HIO DEVELOPMENT OVER TIME. THIS INFORMATION WILL BE VALUABLE TO EVALUATE HOW SIMILAR (OR DISSIMILAR) IN VITRO ORGANOID DEVELOPMENT IS TO EMBRYONIC AND FETAL HEART AND INTESTINE DEVELOPMENT AND GUIDE NEW INTERVENTIONS TO IMPROVE ORGANOID MODELING OF HUMAN DEVELOPMENT.