Correction of rotational distortion for catheter-based en face OCT and OCT angiography

We demonstrate a computationally efficient method for correcting the nonuniform rotational distortion (NURD) in catheter-based imaging systems to improve endoscopic en face optical coherence tomography (OCT) and OCT angiography. The method performs nonrigid registration using fiducial markers on the catheter to correct rotational speed variations. Algorithm performance is investigated with an ultrahigh-speed endoscopic OCT system and micromotor catheter. Scan nonuniformity is quantitatively characterized, and artifacts from rotational speed variations are significantly reduced. Furthermore, we present endoscopic en face OCT and OCT angiography images of human gastrointestinal tract in vivo to demonstrate the image quality improvement using the correction algorithm.National Institutes of Health (U.S.) (R01-EY011289-26)National Institutes of Health (U.S.) (R44-EY022864-01)National Institutes of Health (U.S.) (R01-CA075289-16)National Institutes of Health (U.S.) (R44-CA101067-05)National Institutes of Health (U.S.) (R01-CA178636-02)United States. Air Force Office of Scientific Research (Contract FA9550-10-1-0063)United States. Air Force Office of Scientific Research (Contract FA9550-12-1-0499

Ultrahigh speed endoscopic swept source optical coherence tomography using a VCSEL light source and micromotor catheter

We developed an ultrahigh speed endoscopic swept source optical coherence tomography (OCT) system for clinical gastroenterology using a vertical-cavity surface-emitting laser (VCSEL) and micromotor based imaging catheter, which provided an imaging speed of 600 kHz axial scan rate and 8 μm axial resolution in tissue. The micromotor catheter was 3.2 mm in diameter and could be introduced through the 3.7 mm accessory port of an endoscope. Imaging was performed at 400 frames per second with an 8 μm spot size using a pullback to generate volumetric data over 16 mm with a pixel spacing of 5 μm in the longitudinal direction. Three-dimensional OCT (3D-OCT) imaging was performed in patients with a cross section of pathologies undergoing standard upper and lower endoscopy at the Veterans Affairs Boston Healthcare System (VABHS). Patients with Barrett’s esophagus, dysplasia, and inflammatory bowel disease were imaged. The use of distally actuated imaging catheters allowed OCT imaging with more flexibility such as volumetric imaging in the terminal ileum and the assessment of the hiatal hernia using retroflex imaging. The high rotational stability of the micromotor enabled 3D volumetric imaging with micron scale volumetric accuracy for both en face and cross-sectional imaging. The ability to perform 3D OCT imaging in the GI tract with microscopic accuracy should enable a wide range of studies to investigate the ability of OCT to detect pathology as well as assess treatment response.National Institutes of Health (U.S.) (R44EY022864-01)National Institutes of Health (U.S.) (R01-CA75289-17)National Institutes of Health (U.S.) (R44-CA101067-06)National Institutes of Health (U.S.) ( R01-EY011289-27)National Institutes of Health (U.S.) (R01-HL095717-04)National Institutes of Health (U.S.) (R01-NS057476-05)United States. Air Force Office of Scientific Research (FA9550-10-1-0063)United States. Air Force Office of Scientific Research. Medical Free Electron Laser Program (FA9550-10-1-0551)German Research Foundation (DFG-GSC80-SAOT)German Research Foundation (DFG-HO-1791/11-1)Center for Integration of Medicine and Innovative Technolog

Diagnostic Imaging and Assessment Using Angle Resolved Low Coherence Interferometry

<p>The redistribution of incident light into scattered fields ultimately limits the ability to image into biological media. However, these scattered fields also contain information about the structure and distribution of protein complexes, organelles, cells and whole tissues that can be used to assess the health of tissue or to enhance imaging contrast by excluding confounding signals. The interpretation of scattered fields depends on a detailed understanding of the scattering process as well as sophisticated measurement systems. In this work, the development of new instruments based on low coherence interferometry (LCI) is presented in order to perform precise, depth-resolved measurements of scattered fields. Combined with LCI, the application of new light scattering models based on both analytic and numerical methods is presented in order to interpret scattered field measurements in terms of scatterer geometry and tissue health. </p><p>The first portion of this work discusses the application of a new light scattering model to the measurement recorded with an existing technique, Angle Resolved Low Coherence Interferometry (a/LCI). In the a/LCI technique, biological samples are interrogated with collimated light and the energy per scattering angle at each depth in the volume is recorded interferometrically. A light scattering model is then used to invert the scattering measurements and measure the geometry of cell nuclei. A new light scattering model is presented that can recover information about the size, refractive index, and for the first time, shape of cell nuclei. This model is validated and then applied to the study of cell biology in a series of experiments measuring cell swelling, cell deformation, and finally detecting the onset of apoptosis.</p><p>The second portion of this work introduces an improved version of a/LCI based on two dimension angle resolved measurement (2D a/LCI) and Fourier domain low coherence interferometry (FD-LCI). Several systems are presenting for high speed and polarization-resolved measurements of scattered fields. An improved light scattering model based on fully polarization and solid angle resolved measurements is presented, and then efficiently implemented using distributed computing techniques. The combined system is validated with phantoms and is shown to be able to uniquely determine the size and shape of scattering particles using a single measurement.</p><p>The third portion of this work develops the use of angle-resolved interferometry for imaging through highly scattering media by exploiting the tendency of scatterers to forward scatter light. A new interferometers is developed that can image through very large numbers of scattering events with acceptable resolution. A computational model capable of reproducing experimental measurements is developed and used to understand the performance of the technique.</p><p>The final portion of the work develops a method for processing 2D angle resolved measurements using optical autocorrelation. In this method, measurements over a range of angles are fused into a single depth scan that incorporates the component of scattered light only from certain spatial scales. The utility of the technique is demonstrated using a gene knockout model of retinal degeneration in mice. Optical autocorrelation is shown to be a potentially useful biomarker of tissue disease.</p>Dissertatio

Endoscopic Optical Coherence Angiography Enables 3-Dimensional Visualization of Subsurface Microvasculature

Endoscopic imaging technologies such as confocal laser endomicroscopy and narrow band imaging (NBI) have been used to investigate vascular changes as hallmarks of early cancer in the gastrointestinal tract. However, the limited frame rate and field of view make confocal laser endomicroscopy imaging sensitive to motion artifacts, whereas NBI has limited resolution and visualizes only the surface vascular pattern. Endoscopic optical coherence tomography (OCT) enables high-speed volumetric imaging of subsurface features at near-microscopic resolution, and can image microvasculature without exogenous contrast agents, such as fluorescein, which obliterates the image in areas of bleeding, or after biopsies and resections. OCT has been used for visualizing microvasculature in small animal models and larger vasculature in swine; however, the speed, resolution, and stability of previous systems were not sufficient for 3-dimenstional visualization of microvasculature in endoscopic clinical applications. Herein, we have presented an ultra–high-speed endoscopic OCT technology that achieves >10 times faster imaging speed than commercial systems and high frame-to-frame stability, enabling OCT angiography in the human gastrointestinal tract. Endoscopic OCT angiography of normal esophagus, nondysplastic Barrett’s esophagus (BE) and normal rectoanal junction are demonstrated.National Institutes of Health (U.S.) (R01-CA75289-16)National Institutes of Health (U.S.) (R44-CA101067-06)National Institutes of Health (U.S.) (R44EY022864-01)National Institutes of Health (U.S.) (R01-EY011289-27)National Institutes of Health (U.S.) (R01-CA178636-01)National Institutes of Health (U.S.) (R01-HL095717-04)United States. Air Force Office of Scientific Research (FA9550-12-1-0499)United States. Air Force Office of Scientific Research (FA9550-10-1-0551

Ultrahigh speed endoscopic swept source optical coherence tomography using a VCSEL light source and micromotor catheter

We developed an ultrahigh speed endoscopic swept source optical coherence tomography (OCT) system for clinical gastroenterology using a vertical-cavity surface-emitting laser (VCSEL) and micromotor based imaging catheter, which provided an imaging speed of 600 kHz axial scan rate and 8 μm axial resolution in tissue. The micromotor catheter was 3.2 mm in diameter and could be introduced through the 3.7 mm accessory port of an endoscope. Imaging was performed at 400 frames per second with an 8 μm spot size using a pullback to generate volumetric data over 16 mm with a pixel spacing of 5 μm in the longitudinal direction. Three-dimensional OCT (3D-OCT) imaging was performed in patients with a cross section of pathologies undergoing standard upper and lower endoscopy at the Veterans Affairs Boston Healthcare System (VABHS). Patients with Barrett’s esophagus, dysplasia, and inflammatory bowel disease were imaged. The use of distally actuated imaging catheters allowed OCT imaging with more flexibility such as volumetric imaging in the terminal ileum and the assessment of the hiatal hernia using retroflex imaging. The high rotational stability of the micromotor enabled 3D volumetric imaging with micron scale volumetric accuracy for both en face and cross-sectional imaging. The ability to perform 3D OCT imaging in the GI tract with microscopic accuracy should enable a wide range of studies to investigate the ability of OCT to detect pathology as well as assess treatment response.National Institutes of Health (U.S.) (R44EY022864-01)National Institutes of Health (U.S.) (R01-CA75289-17)National Institutes of Health (U.S.) (R44-CA101067-06)National Institutes of Health (U.S.) ( R01-EY011289-27)National Institutes of Health (U.S.) (R01-HL095717-04)National Institutes of Health (U.S.) (R01-NS057476-05)United States. Air Force Office of Scientific Research (FA9550-10-1-0063)United States. Air Force Office of Scientific Research. Medical Free Electron Laser Program (FA9550-10-1-0551)German Research Foundation (DFG-GSC80-SAOT)German Research Foundation (DFG-HO-1791/11-1)Center for Integration of Medicine and Innovative Technolog