Guillermo J. Tearney

Optical coherence tomography-guided laser marking with tethered capsule endomicroscopy (Conference Presentation)

Tethered capsule endomicroscopy (TCE) is a new method for performing comprehensive microstructural OCT imaging of gastrointestinal (GI) tract in unsedated patients in a well-tolerated and cost-effective manner. These features of TCE bestow it with significant potential to improve the screening, surveillance and management of various upper gastrointestinal diseases. To achieve clinical adoption of this imaging technique, it is important to validate it with co-registered histology, the current diagnostic gold standard. One such method for co-registering OCT images with histology is laser cautery marking, previously demonstrated using a balloon-centering OCT catheter that operates in conjunction with sedated endoscopy. With laser marking, an OCT area of interest is identified on the screen and this target is marked in the patient by exposing adjacent tissue to laser light that is absorbed by water, creating superficial, visible marks on the mucosal surface. Endoscopy can then be performed after the device is removed and biopsies taken from the marks. In this talk, we will present the design of a tethered capsule laser marking device that uses a distal stepper motor to perform high precision (< 0.5 mm accuracy) laser targeting and high quality OCT imaging. Ex vivo animal tissue tests and pilot human clinical studies using this technology will be presented.

Micro optical coherence tomography probe for high resolution imaging of the inner ear (Conference Presentation)

Sensorineural hearing loss (SNHL) is the most common sensory deficit in the world, caused by damage to cellular structures within the inner ear, or cochlea. Visualization of the cellular pathology underlying different types of SNHL has been difficult due to the small size of the cochlea, its complex three-dimensional structure, and embedded location within the temporal bone. Micro-optical coherence tomography (µOCT) is a recently-developed cross-sectional imaging technology that can obtain images with sufficient detail to elucidate specific aetiologies of SNHL. In this work, we developed a high resolution, ultra-small-diameter, flexible probe for imaging the human cochlea in situ. The 500 µm diameter, circumferential scanning µOCT imaging probe contains self-imaging wavefront division optics that provide maximal lateral resolution of 2.5 µm and better than 5 µm resolution over an extended depth of focus of 1 mm in air. Using a supercontinuum light source with a 300 nm bandwidth and a common path interferometery configuration, axial resolution is 1.9 µm in air. Images of 3D-intact cochleae extracted from human cadavers were acquired with the µOCT probe in situ; these images demonstrate the system’s ability to visualize the entire cross-section of the scala tympani, in addition to cellular structures in the cochlea’s sensory epithelium, the organ of Corti and bundles of auditory nerves. These results suggest that this new device has the potential to facilitate personalized diagnosis and therapy for SNHL.

Trans-nasal OCT imaging of the small intestine (Conference Presentation)

Environmental enteric dysfunction (EED) is a poorly understood condition of the small intestine prevalent in low and middle income countries. This disease is believed to cause nutrient malabsorption and poor oral vaccine uptake, resulting in arrested neurological development and growth stunting in children that persists as they grow into adulthood. Optical coherence tomography (OCT) imaging of the small intestine can potentially capture some of the microstructural changes, such as villous blunting, in the small gut that accompany EED, and hence could potentially improve the understanding of EED and help in determining and monitoring the effectiveness of EED interventions. Notably, EED must be studied and diagnosed in infants, aged 0-24 months as this is the only window in which interventional strategies can reverse the disease. In order to address this need, we propose a trans-nasal OCT imaging technique for imaging the small intestine that may be suitable for low-resource settings owing to its simplicity, ease of administration, and implementation in unsedated infants. To demonstrate the potential of transnasal OCT intestinal imaging, we have created a 10 Fr transnasal OCT imaging probe and have submitted an IRB application for a first-in-human study using this probe to image the adult small intestine. We anticipate that the results from this pilot study will justify the development of a transnasal OCT intestinal imaging device for infants.

Cellular-resolution, extended depth of focus optical coherence tomography catheter toward in vivo cardiovascular imaging (Conference Presentation)

Optical coherence tomography (OCT) has been a useful clinical tool for diagnosing coronary artery disease through a flexible catheter, but its full promise relies on resolving cellular and sub-cellular structures in vivo. Previously, visualizing cellular structures through an imaging catheter is not possible due to limited depth of focus (DOF) of a tightly focused Gaussian beam: typically, a Gaussian beam with 2-3 μm resolution has a DOF within 100 μm, which is not sufficient for in vivo catheter imaging. Therefore, we developed a self-imaging wavefront division optical system that generates a coaxially-focused multimode (CAFM) beam with a DOF that is approximately one order of magnitude longer than that of a Gaussian beam. In this study, we present a high-resolution, extended DOF catheter based on self-imaging wavefront division optics. The catheter generates a CAFM beam with a lateral resolution of 3 μm and a DOF close to 2 mm. To correct the aberration introduced by catheter sheath, we incorporated a cylindrical prism to compensate the sheath astigmatism. When the catheter is incorporated into a micro-resolution OCT (μOCT) system with rotational scanning mechanics, cellular-resolution cross-sectional images of the coronary artery wall can be obtained. The device serves as an important step toward characterizing cellular and sub-cellular structures in vivo for coronary artery disease diagnosis.