Tethered capsule endomicroscopy (TCE) is a recently developed form of in vivo microscopy based on optical coherence tomography (OCT). With TCE, a small tethered pill is swallowed, procuring high resolution microscopic images of the esophageal wall. TCE does not require sedation and is thus a more rapid and convenient procedure comparing to traditional endoscopic examination. Our group and others have successfully conducted OCT-TCE in pilot, single-center studies that demonstrated the potential of this technology for upper GI tract diagnosis. Here, we demonstrate and evaluate the feasibility and safety of a next generation OCT-TCE system and device in patients with Barrett’s esophagus (BE) and report the initial longitudinal analysis of the natural history of BE.
While the most common method used to evaluate and survey patients with Barrett’s Esophagus (BE) is endoscopic biopsy, this procedure is invasive, time-consuming, and suffers from sampling errors. Moreover, it requires patient sedation that increases cost and mandates its operation in specialized settings. Our lab has developed a new imaging tool termed tethered capsule endomicroscopy (TCE) that involves swallowing a tethered capsule which utilizes optical coherence tomography (OCT) to obtain three-dimensional microscopic (10µm) images of the entire esophageal wall as it traverses the luminal organ via peristalsis or is retrieved by pulling up tether. As opposed to endoscopy, TCE procedure is non-invasive, doesn’t require patient sedation and mitigates sampling error by evaluating the microscopic structure of the entire esophagus. The merits of TCE make it a suitable device to investigate the microscopic natural history of BE in a longitudinal manner.
Here, we present our initial experience of a multicenter (5-site) clinical trial to study the microscopic natural history of BE. The TCE device used for the study is the new generation capsule with the ball lens optical configuration and a distal scan stepper motor, which provides 30µm (lateral) resolution and 40Hz imaging rate. The portable OCT imaging system is a custom in-house built swept source system and provides 7µm (axial) at a 100 kHz A-line rate with a center wavelength of ~1310 nm. To date, we have successfully enrolled 69 subjects at all sites (MGH: 33, Columbia University: 11, Kansas City VA: 10, Mayo Jacksonville: 8, Mayo Rochester: 7) and 59 have swallowed the capsule (85.5%). There have been no reported adverse events associated with TCE procedure. High-quality OCT images were reliably obtained from patients who swallowed the device, and BE tissues were identified by expert readers. Our initial experience with TCE in a multicenter study demonstrates that this technology is easy to use and efficient in multiple clinical settings. Completion of this longitudinal study is likely to provide new insights on the temporal progression of BE that may impact management strategies.
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.
Conventional OCT images, obtained using a focused Gaussian beam have a lateral resolution of approximately 30 μm and a depth of focus (DOF) of 2-3 mm, defined as the confocal parameter (twice of Gaussian beam Rayleigh range). Improvement of lateral resolution without sacrificing imaging range requires techniques that can extend the DOF. Previously, we described a self-imaging wavefront division optical system that provided an estimated one order of magnitude DOF extension. In this study, we further investigate the properties of the coaxially focused multi-mode (CAFM) beam created by this self-imaging wavefront division optical system and demonstrate its feasibility for real-time biological tissue imaging. Gaussian beam and CAFM beam fiber optic probes with similar numerical apertures (objective NA≈0.5) were fabricated, providing lateral resolutions of approximately 2 μm. Rigorous lateral resolution characterization over depth was performed for both probes. The CAFM beam probe was found to be able to provide a DOF that was approximately one order of magnitude greater than that of Gaussian beam probe. By incorporating the CAFM beam fiber optic probe into a μOCT system with ~1.5 μm axial resolution, we were able to acquire cross-sectional images of swine small intestine ex vivo, enabling the visualization of subcellular structures, providing high quality OCT images over more than a 300 μm depth range.
Intracranial aneurysms affect a large number of individuals every year. Changes to hemodynamics are thought to be a crucial factor in the initial formation and enlargement of intracranial aneurysms. Previously, surgical clipping – an open an invasive procedure, was the standard of care. More recently, minimally invasive, catheter based therapies, specifically stenting and coiling, has been employed for treatment as it is less invasive and poses fewer overall risks. However, these treatments can further alter hemodynamic patterns of patients, affecting efficacy and prognosis.
Doppler optical coherence tomography (DOCT) has shown to be useful for the evaluation of changes to hemodynamic patterns in various vascular pathologies, and intravascular DOCT may provide useful insight in the evaluation and changes to hemodynamic patterns before and during the treatment of aneurysms.
In this study, we present preliminary results of DOCT imaging used in three patient-specific aneurysm phantoms located within the Circle of Willis both pre and post-treatment. These results are compared with computational fluid dynamics (CFD) simulations and high-speed camera imaging for further interpretation and validation of results.
Endovascular Optical Coherence Tomography (OCT) has previously been used in both bench-top and clinical environments to produce vascular images, and can be helpful in characterizing, among other pathologies, plaque build-up and impedances to normal blood flow. The raw data produced can also be processed to yield high-resolution blood velocity information, but this computation is expensive and has previously only been available a posteriori using post-processing software. Real-time Doppler OCT (DOCT) imaging has been demonstrated before in the skin and eye, but this capability has not been available to vascular surgeons.
Graphics Processing Units (GPUs) can be used to dramatically accelerate this type of distributed computation. In this paper we present a software package capable of real-time DOCT processing and circular image display using GPU acceleration designed to operate with catheter-based clinical OCT systems. This image data is overlayed onto structural images providing clinicians with live, high-resolution blood velocity information to complement anatomical data.
Further, we validated flow data obtained in real time using a carotid flow phantom -- constructed using 3D structural OCT data -- and controlled flow from an external pump.
Endoscopy, the current standard of care for the diagnosis of upper gastrointestinal (GI) diseases, is not ideal as a screening tool because it is costly, necessitates a team of medically trained personnel, and typically requires that the patient be sedated. Endoscopy is also a superficial macroscopic imaging modality and therefore is unable to provide detailed information on subsurface microscopic structure that is required to render a precise tissue diagnosis. We have overcome these limitations through the development of an optical coherence tomography tethered capsule endomicroscopy (OCT-TCE) imaging device. The OCT-TCE device has a pill-like form factor with an optically clear wall to allow the contained opto-mechanical components to scan the OCT beam along the circumference of the esophagus. Once swallowed, the OCT-TCE device traverses the esophagus naturally via peristalsis and multiple cross-sectional OCT images are obtained at 30-40 μm lateral resolution by 7 μm axial resolution. While this spatial resolution enables differentiation of squamous vs columnar mucosa, crucial microstructural features such as goblet cells (~10 μm), which signify intestinal metaplasia in BE, and enlarged nuclei that are indicative of dysplasia cannot be resolved with the current OCT-TCE technology.
In this work we demonstrate a novel design of a high lateral resolution OCT-TCE device with an extended depth of focus (EDOF). The EDOF is created by use of self-imaging wavefront division multiplexing that produces multiple focused modes at different depths into the sample. The overall size of the EDOF TCE is similar to that of the previous OCT-TCE device (~ 11 mm by 26 mm) but with a lateral resolution of ~ 8 μm over a depth range of ~ 2 mm. Preliminary esophageal and intestinal imaging using these EDOF optics demonstrates an improvement in the ability to resolve tissue morphology including individual glands and cells. These results suggest that the use of EDOF optics may be a promising avenue for increasing the accuracy of OCT-TCE for the diagnosis of upper GI diseases.
Endovascular Optical Coherence Tomography (OCT) has previously been used in both bench-top and clinical environments to produce vascular images, and can be helpful in characterizing, among other pathologies, plaque build-up and impedances to normal blood ow. The raw data produced can also be processed to yield high- resolution blood velocity information, but this computation is expensive and has previously only been available a posteriori using post-processing software. Real-time Doppler OCT (DOCT) imaging has been demonstrated before in the skin and eye, but this capability has not been available to vascular surgeons. Graphics Processing Units (GPUs) can be used to dramatically accelerate this type of distributed computation. In this paper we present a software package capable of real-time DOCT processing and circular image display using GPU acceleration designed to operate with catheter-based clinical OCT systems. This image data is overlayed onto structural images providing clinicians with live, high-resolution blood velocity information to complement anatomical data.
Carotid atherosclerosis is a critical medical concern that can lead to ischemic stroke. Local hemodynamic patterns
have also been associated with the development of atherosclerosis, particularly in regions with disturbed flow
patterns such as bifurcations. Traditionally, this disease was treated using carotid endarterectomy, however
recently there is an increasing trend of carotid artery stenting due to its minimally invasive nature. It is well
known that this interventional technique creates changes in vasculature geometry and hemodynamic patterns
due to the interaction of stent struts with arterial lumen, and is associated with complications such as distal
emboli and restenosis. Currently, there is no standard imaging technique to evaluate regional hemodynamic
patterns found in stented vessels.
Doppler optical coherence tomography (DOCT) provides an opportunity to identify in vivo hemodynamic
changes in vasculature using high-resolution imaging. In this study, blood flow profiles were examined at the
bifurcation junction in the internal carotid artery (ICA) in a porcine model following stent deployment. Doppler
imaging was further conducted using pulsatile flow in a phantom model, and then compared to computational
fluid dynamics (CFD) simulation of a virtual bifurcation to assist with the interpretation of emphin vivo results.
The use of gas assistance in laser machining hard materials is well established in manufacturing but not in the context of surgery. Laser cutting of osseous tissue in the context of neurosurgery can benefit from gas-assist but requires an understanding of flow and pressure effects to minimize neural tissue damage. In this study we acquire volumetric flow rates through a gas nozzle on the spinal cord, with dura and without dura.
This study presents the design of a system used to monitor laser ablation in real-time using Optical Coherence Tomography (OCT). The design of the system involves a high-powered fiber laser (wavelength of 1064nm, 1kW peak power) being built directly into the sample arm of the OCT system (center wavelength 1310). It is shown that the OCT laser light and subsequent backscatter pass relatively unaffected through the fiber laser. Initial results are presented showing monitoring of the ablation process at a single point in real time using m-mode imaging.
This paper presents the development of a compact, desktop laser-cutting system capable of cutting materials such as wood, metal and plastic. A re-commissioned beheaded MakerBot® Replicator 2X is turned into a 3-DOF laser cutter by way of integration with 800W (peak power) fiber laser. Special attention is paid to tear-down, modification and integration of the objective lens in place of the print head. Example cuts in wood and metal will be presented, as well as design of an exhaust system.
The hemodynamic environment is known to play a crucial role in the progression, rupture, and treatment of intracranial aneurysms. Currently there is difficulty assessing and measuring blood flow profiles in vivo. An emerging high resolution imaging modality known as split spectrum Doppler optical coherence tomography (ssDOCT) has demonstrated the capability to quantify hemodynamic patterns as well as arterial microstructural changes. In this study, we present a novel in vitro method to acquire precise blood flow patterns within a patient- specific aneurysm silicone flow models using ssDOCT imaging. Computational fluid dynamics (CFD) models were generated to verify ssDOCT results.
Kyle Cheng, Adrian Mariampillai, Kenneth Lee, Barry Vuong, Timothy Luk, Joel Ramjist, M. Anne Curtis, Henry Jakubovic, Peter Kertes, Michelle Letarte, Marie Faughnan, Victor Yang
Speckle statistics of flowing scatterers have been well documented in the literature. Speckle variance optical coherence tomography exploits the large variance values of intensity changes in time caused mainly by the random backscattering of light resulting from translational activity of red blood cells to map out the microvascular networks. A method to map out the microvasculature malformation of skin based on the time-domain histograms of individual pixels is presented with results obtained from both normal skin and skin containing vascular malformation. Results demonstrated that this method can potentially map out deeper blood vessels and enhance the visualization of microvasculature in low signal regions, while being resistant against motion (e.g., patient tremor or internal reflex movements). The overall results are manifested as more uniform en face projection maps of microvessels. Potential applications include clinical imaging of skin vascular abnormalities and wide-field skin angiography for the study of complex vascular networks.
The electric field induced optical changes (EIOC) measured by the optical coherence tomography (OCT) reflect the local electro-kinetic properties of the tissue. In this study we developed a method to use the phase of the complex OCT images to map EIOC in tissue samples. Switching the polarity of the electric field induced significant reversible changes in the phase of the complex OCT images. Since the resulting phase was degraded by the noise an advanced signal processing algorithm was developed to obtain the EIOC images. The developed algorithm made it possible to get structural phase images from a standard commercial OCT system, potentially yielding important insights into the local electro-kinetic properties of the tissue. We use a simple theoretical model to simulate main features of amplitude and phase EIOC observed using frequency-domain OCT.
Optical coherence elastography (OCE) provides deformation or material properties, mapping of soft tissue. We aim to develop a robust speckle tracking OCE technique with improved resolution and accuracy. A digital image correlation (DIC)-based OCE technique was developed by combining an advanced DIC algorithm with optical coherence tomography (OCT). System calibration and measurement error evaluation demonstrated that this DIC-based OCE technique had a resolution of ∼0.6 μm displacement and <0.5% strain measurement in the axial scan direction. The measured displacement ranged from 0.6 to 150 μm, obtained via phantom imaging. The capability of the DIC-based OCE technique, for differentiation of stiffness, was evaluated by imaging a candle gel phantom with an irregularly shaped stiff inclusion. OCE imaging of a chicken breast sample differentiated the fat, membrane, and muscle layers. Strain elastograms of an aneurysm sample showed heterogeneity of the tissue and clear contrast between the adventitia and media. These promising results demonstrated the capability of the DIC-based OCE for the characterization of the various components of the tissue sample. Further improvement of the system will be conducted to make this OCE technique a practical tool for measuring and differentiating material properties of soft tissue.
Optical coherence elastography (OCE) provides deformation or material properties mapping of soft tissue, which is
important for morphological and pathological studies of the tissue. An OCE technique is developed based on digital
image correlation. System calibration and measurement error evaluation are performed. The displacement measurement
of 0.6 μm to over 100 μm was obtained through a phantom experiment. The capability of this OCE technique for
differentiation of stiffness was evaluated by imaging a two-components phantom. OCE imaging of an aneurysm sample
shows promising results for characterization of composites of aneurismal wall in the future.
High-resolution mapping of microvasculature has been applied to diverse body systems, including the retinal and choroidal vasculature, cardiac vasculature, the central nervous system, and various tumor models. Many imaging techniques have been developed to address specific research questions, and each has its own merits and drawbacks. Understanding, optimization, and proper implementation of these imaging techniques can significantly improve the data obtained along the spectrum of unique research projects to obtain diagnostic clinical information. We describe the recently developed algorithms and applications of two general classes of microvascular imaging techniques: speckle-variance and phase-variance optical coherence tomography (OCT). We compare and contrast their performance with Doppler OCT and optical microangiography. In addition, we highlight ongoing work in the development of variance-based techniques to further refine the characterization of microvascular networks.
We have measured changes in optical coherence signals during the application of an external electric field to tissue samples. We employed the swept-source OCT engine with a broadband light source of 140-nm spectral bandwidth centered at 1300 nm. Switching the polarity of the electric field induced significant reversible changes in the phase of the OCT signal. Since the phase signal was corrupted by phase noise, it required a formidable signal processing to obtain the images of electrically induced phase changes.
Blood flow velocity and volumetric flow measurements are important parameters for assessment of the severity of stenosis and the outcome of interventional therapy. However, feasibility of intravascular flow measurement using a rotational catheter based phase resolved Doppler optical coherence tomography (DOCT) is difficult. Motion artefacts induced by the rotating optical imaging catheter, and the radially dependent noise background of measured Doppler signals are the main challenges encountered. In this study, a custom-made data acquisition system and developed algorithms to remove non-uniform rotational distortion (NURD) induced phase shift artefact by tracking the phase shift observed on catheter sheath. The flow velocity is calculated from Doppler shift obtained by Kasai autocorrelation after motion artefact removal. Blood flow velocity profiles in porcine carotid arteries in vivo were obtained at 100 frames/s with 500 A-lines/frame and DOCT images were taken at 20 frames/s with 2500 A-lines/frame. Time-varying velocity profiles were obtained at an artery branch. Furthermore, the identification of a vein adjacent to the catheterized vessel based on the color Doppler signal was also observed. The absolute measurement of intravascular flow using a rotating fiber catheter can provide insights to different stages of interventional treatment of stenosis in carotid artery.
Rupture of intracranial aneurysm is a common cause of subarachnoid hemorrhage. An aneurysm may undergo
microscopic morphological changes or remodeling of the vessel wall prior to rupture, which could potentially be
imaged. In this study we present methods of tissue sample preparation of intracranial aneurysms and correlation
between optical coherence tomography imaging and routine histology. OCT has a potential future in the
assessment of microscopic features of aneurysms, which may correlate to the risk of rupture.
A prototype neurosurgical hand-held optical coherence tomography (OCT) imaging probe has been developed to provide
micron resolution cross-sectional images of subsurface tissue during open surgery. This new ergonomic hand-held probe
has been designed based on our group's previous work on electrostatically driven optical fibers. It has been packaged
into a catheter probe in the familiar form factor of the clinically accepted Bayonet shaped neurosurgical non-imaging
Doppler ultrasound probes. The optical design was optimized using ZEMAX simulation. Optical properties of the probe
were tested to yield an ~20 um spot size, 5 mm working distance and a 3.5 mm field of view. The scan frequency can be
increased or decreased by changing the applied voltage. Typically a scan frequency of less than 60Hz is chosen to keep
the applied voltage to less than 2000V. The axial resolution of the probe was ~15 um (in air) as determined by the OCT
system. A custom-triggering methodology has been developed to provide continuous stable imaging, which is crucial for
clinical utility. Feasibility of this probe, in combination with a 1310 nm swept source OCT system was tested and images
are presented to highlight the usefulness of such a forward viewing handheld OCT imaging probe. Knowledge gained
from this research will lay the foundation for developing new OCT technologies for endovascular management of
cerebral aneurysms and transsphenoidal neuroendoscopic treatment of pituitary tumors.
In this study, a cascaded Raman fiber laser in Fourier domain mode lock operation (FDML) is presented. This
laser utilizes a Ytterbium doped twin core pump laser source at 1109 nm. The pump light is directed to a
cascaded Raman cavity, which consists of multiple cascaded fiber Bragg grating pairs and 3.86 km of dispersion
compensation fiber, which provides Raman gain. The output wavelength of a cascaded Raman laser is determined
by the Stoke's shift (≈ 60 to 70 nm in optical fiber) and the pump laser wavelength. The power build up in the
cascaded Raman cavity and shift to higher Stoke's orders produce multiple spectral peaks. At higher Stoke's
orders, the overlapping Raman peaks create broad bandwidth gain with relatively large gain ripples. FDML
operation using a polygon-based tunable filter helps to suppress the ripples. The overall laser in linear operation
has a bandwidth of 316 nm with a center wavelength of 1445 nm. An output optical power was measured to be
(> 10 mW). On the other hand, the sweeping bandwidth was 35 nm with an output power in the micro-watt
range. The utilization of broadband tunable lasers are important in applications such as swept-source optical
coherence tomography for use in biomedical imaging.
We demonstrate high efficiency and wide bandwidth gain in a Ytterbium doped fiber amplifier. The highpowered
amplifier has potential applications for use with a swept-source fiber ring laser in multi-channel optical
coherence tomography (OCT) system. The ring cavity design includes a 976nm pumped dual core Yb doped fiber as the
gain medium, where a rotating polygon mirror is used as a wavelength-sweeping filter for this source. The amplified
spontaneous emission (ASE) had a spectral bandwidth of 1037-1145nm at -60dBm, where a tunable lasing bandwidth of
the ring cavity ranged from 1057-1115nm. The highest output power, for both the ASE and lasing spectrum, with this
configuration was ~200mW, however it is possible to have a larger bandwidth and a larger output power. Higher power,
in the wattage range is achievable if free space components are employed. Pumped with 976nm light at 1.27W, the use
of this novel dual core Yb doped fiber as an amplifier has been successfully demonstrated, as it provided a small signal
gain of 29.6 dB at 1085nm, where the gain medium was successfully saturated during operation. This is important for the
spectral shaping requirements of OCT to improve image quality. The gain was demonstrated for several different
wavelengths and for several pumping powers at a 1085nm wavelength. Fourier domain mode locked operation (FDML)
was achieved with a bandwidth of 15nm and a sweep rate of 51.4kHz. This laser source offers a low-cost, high power
alternative for biomedical imaging with multi-channel optical coherence tomography.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.