Endoscopic Optical Coherence Tomography Research Articles

Early Detection of Carcinoma In Situ of the Bladder: A Comparative Study of White Light Cystoscopy, Narrow Band Imaging, 5-ALA Fluorescence Cystoscopy and 3-Dimensional Optical Coherence Tomography

We compared the efficacy and potential limitations of white light cystoscopy, narrow band imaging, 5-ALA fluorescence cystoscopy and 3-dimensional optical coherence tomography for early diagnosis of bladder carcinoma in situ. By expressing simian virus 40T antigen in the urothelium carcinoma in situ typically develops in SV40T transgenic mice in about 8 to 20 weeks and then frank high grade papillary urothelial carcinoma starts to emerge. A total of 18 control and 29 SV40T mice were examined during weeks 8 to 22 by white light cystoscopy, fluorescence cystoscopy, narrow band imaging and 3-dimensional optical coherence tomography. Results were validated by histology. Newly improved algorithms for computer aided detection were applied to acquired 3-dimensional optical coherence tomography images to enhance the quantitative diagnosis of carcinoma in situ in near real time. Of 29 carcinoma in situ samples 27 were detected by 3-dimensional optical coherence tomography, 1 by white light cystoscopy, 26 by narrow band imaging and 13 by fluorescence cystoscopy. Of the 18 histologically confirmed benign cases 17 were detected by 3-dimensional optical coherence tomography, 14 by white light cystoscopy, 5 by narrow band imaging and 18 by fluorescence cystoscopy. The diagnostic sensitivity of white light cystoscopy (3.4%) and fluorescence cystoscopy (44.8%), and the specificity of narrow band imaging (27.8%) were significantly enhanced by 3-dimensional optical coherence tomography to 93.1% and 94.4%, respectively (p <0.01). Three-dimensional optical coherence tomography with quantitative computer aided detection can significantly enhance the sensitivity of white light cystoscopy and fluorescence cystoscopy, and the specificity of narrow band imaging for early diagnosis of carcinoma in situ. This suggests the potential of narrow band imaging guided 3-dimensional optical coherence tomography for future clinical detection of carcinoma in situ when effective image guidance is desirable.

Comparison of Tissue Architectural Changes between Radiofrequency Ablation and Cryospray Ablation in Barrett’s Esophagus Using Endoscopic Three-Dimensional Optical Coherence Tomography

Two main nonsurgical endoscopic approaches for ablating dysplastic and early cancer lesions in the esophagus have gained popularity, namely, radiofrequency ablation (RFA) and cryospray ablation (CSA). We report a uniquely suited endoscopic and near-microscopic imaging modality, three-dimensional (3D) optical coherence tomography (OCT), to assess and compare the esophagus immediately after RFA and CSA. The maximum depths of architectural changes were measured and compared between the two treatment groups. RFA was observed to induce 230~260 μm depth of architectural changes after each set of ablations over a particular region, while CSA was observed to induce edema-like spongiform changes to ~640 μm depth within the ablated field. The ability to obtain micron-scale depth-resolved images of tissue structural changes following different ablation therapies makes 3D-OCT an ideal tool to assess treatment efficacy. Such information could be potentially used to provide real-time feedback for treatment dosing and to identify regions that need further retreatment.

Post-tuning of Sample Position in Common-path Swept-source Optical Coherence Tomography

Common-path interferometers are widely used for endoscopic optical coherence tomography (OCT) because an arbitrary arm length can be chosen for the endoscopic imaging probe. However, the scheme suffers from the limited range of the sample position distance from the end of the imaging probe because the position between the reference reflector and the sample is limited by the optical path-length difference (OPD) to induce an interference signal. In this study, we developed a novel method for compensating the arbitrary sample position in common-path swept-source OCT by adding an extra Mach-Zehnder interferometer in the post-path of the interfered optical signal. Theoretical analysis and an experimental demonstration of imaging depth tuning for the flexible sample position of an endoscopic OCT image are discussed. After post-tuning of sample position distance, the positioning limitation between the reference reflector and the sample can be solved for various sample positions over a range of 26 mm for the cross-sectional images of a fish eye sample.

Scanning and Tunable Micro-Optics for Endoscopic Optical Coherence Tomography

The design, fabrication, and integration of micro-optical components for beam focus and steering are demonstrated in an endoscopic optical coherence tomography (OCT) system. The relevant components, a membrane-based microfluidic tunable microlens and an electrostatic 2-D scanning micromirror, are fabricated using silicon and polymer-based microelectromechanical system technologies. All components are assembled inside a 4.5 μm diameter probe. The design of the optical system, including substantiation of the need for focal length tunability, is presented, along with performance data of an OCT system using these components. A lateral resolution of about 13 μm is achieved, an improvement over fixed-focal length probes. Due to the miniaturization of the measurement head achievable using this optical microsystem, use in conventional endoscopes is possible.

Motion artifacts associated with in vivo endoscopic OCT images of the esophagus

3-D optical coherence tomography (OCT) has been extensively investigated as a potential screening and/or surveillance tool for Barrett’s esophagus (BE). Understanding and correcting motion artifact may improve image interpretation. In this work, the motion trace was analyzed to show the physiological origin (respiration and heart beat) of the artifacts. Results showed that increasing balloon pressure did not sufficiently suppress the physiological motion artifact. An automated registration algorithm was designed to correct such artifacts. The performance of the algorithm was evaluated in images of normal porcine esophagus and demonstrated in images of BE in human patients.

Investigating in vivo airway wall mechanics during tidal breathing with optical coherence tomography

Optical coherence tomography (OCT) is a nondestructive imaging technique offering high temporal and spatial resolution, which makes it a natural choice for assessing tissue mechanical properties. We have developed methods to mechanically analyze the compliance of the rabbit trachea in vivo using tissue deformations induced by tidal breathing, offering a unique tool to assess the behavior of the airways during their normal function. Four-hundred images were acquired during tidal breathing with a custom-built endoscopic OCT system. The surface of the tissue was extracted from a set of these images via image processing algorithms, filtered with a bandpass filter set at respiration frequency to remove cardiac and probe motion, and compared to ventilatory pressure to calculate wall compliance. These algorithms were tested on elastic phantoms to establish reliability and reproducibility. The mean tracheal wall compliance (in five animals) was 1.3±0.3×10(-5) (mm Pa)(-1). Unlike previous work evaluating airway mechanics, this new method is applicable in vivo, noncontact, and loads the trachea in a physiological manner. The technique may have applications in assessing airway mechanics in diseases such as asthma that are characterized by significant airway remodeling.

Piezoelectric-transducer-based miniature catheter for ultrahigh-speed endoscopic optical coherence tomography

We developed a piezoelectric-transducer- (PZT) based miniature catheter with an outer diameter of 3.5 mm for ultrahigh-speed endoscopic optical coherence tomography (OCT). A miniaturized PZT bender actuates a fiber and the beam is scanned through a GRIN lens and micro-prism to provide high-speed, side-viewing capability. The probe optics can be pulled back over a long distance to acquire three-dimensional (3D) data sets covering a large area. Imaging is performed with 11 μm axial resolution in air (8 μm in tissue) and 20 μm transverse resolution, at 960 frames per second with a Fourier domain mode-locked laser operating at 480 kHz axial scan rate. Using a high-speed data acquisition system, endoscopic OCT imaging of the rabbit esophagus and colon in vivo and human colon specimens ex vivo is demonstrated.

Characterization of optical fiber imaging bundles for swept-source optical coherence tomography

Fiber imaging bundles have been investigated for use in endoscopic optical coherence tomography (OCT) systems, to obviate the requirement for scanning components within the endoscope probe section. Images have been acquired using several optical configurations, two of which are common path in design. Configurations have been selected as having potential for miniaturization and inclusion in endoscopic-type systems, since the advantages of employing imaging bundles are most clearly seen in this type of system. The various types of bundle available are described, and the properties of the leached bundles used here are discussed in detail, with reference to their effect upon the performance of OCT systems. Images are displayed from measurements made on a range of samples.

Three-dimensional Imaging of Ureter With Endoscopic Optical Coherence Tomography

To verify the ability to identify the layered structures of the ureteral wall and to image a segment of the ureter in 3 dimensions with high-speed, endoscopic optical coherence tomography (EOCT). We imaged a porcine ureter ex vivo using a spectral-domain EOCT with a specially designed circumferential scanning fiber catheter. The images were correlated with the histologic findings to identify the corresponding structures. Three-dimensional images and en face images at different depths from the luminal surface were reconstructed from the multiple cross-sectional images to visualize the layered structure of a segment of the ureter from different perspectives. The EOCT images clearly revealed all layers of the ureteral wall as shown in the histologic images. In particular, with the specially designed fiber catheter, the light beam was well centered during the rotation and pull back, allowing constant acquisition of high-fidelity images and unambiguous identification of the smooth muscle layers in all images. With high-speed EOCT, a segment of ureter (20 mm) can be imaged in <90 seconds at a high resolution. With its ability to visualize all layers of the ureteral wall, EOCT offers the potential to stage urothelial cancers that have infiltrated the muscular wall (Stage T2). This information will be complimentary to the diagnostic information obtained through ureteroscopic biopsy and computed tomography urogram.

Quantification of airway thickness changes in smoke-inhalation injury using in-vivo 3-D endoscopic frequency-domain optical coherence tomography

Smoke inhalation injury is frequently accompanied by cyanide poisoning that may result in substantial morbidity and mortality, and methods are needed to quantitatively determine extent of airway injury. We utilized a 3-D endoscopic frequency-domain optical coherence tomography (FD-OCT) constructed with a swept-source laser to investigate morphological airway changes following smoke and cyanide exposure in rabbits. The thickness of the mucosal area between the epithelium and cartilage in the airway was measured and quantified. 3-D endoscopic FD-OCT was able to detect significant increases in the thickness of the tracheal walls of the rabbit beginning almost immediately after smoke inhalation injuries which were similar to those with combined smoke and cyanide poisoning.

Miniature endoscopic optical coherence tomography probe employing a two-axis microelectromechanical scanning mirror with through-silicon vias

We present the design and experimental results of a new MEMS-based endoscopic optical coherence tomography (OCT) probe. The uniqueness of this miniature OCT imaging probe is a two-axis MEMS mirror with through-silicon vias (TSVs) for interconnecting. The TSV interconnection enables ultracompact probe design, successfully reducing the probe size to only 2.6 mm in diameter. The MEMS mirror is actuated by an electrothermal actuator that is capable of scanning ± 16° at only 3.6 V DC. Two-dimensional and three-dimensional OCT images of microspheres embedded in PDMS and acute rat brain tissue have been obtained with this miniature probe in a time-domain OCT system.

MEMS-Based Endoscopic Optical Coherence Tomography

Early cancer detection has been playing an important role in reducing cancer mortality. Optical coherence tomography (OCT), due to its micron-scale resolution, has the ability to detect cancerous tissues at their early stages. For internal organs, endoscopic probes are needed as the penetration depth of OCT is about 1–3 mm. MEMS technology has the advantages of fast speed, small size, and low cost, and it has been widely used as the scanning engine in endoscopic OCT probes. Research results have shown great potential for OCT in endoscopic imaging by incorporating MEMS scanning mirrors. Various MEMS-OCT designs are introduced, and their imaging results are reviewed in the paper.

Imaging true 3D endoscopic anatomy by incorporating magnetic tracking with optical coherence tomography: proof-of-principle for airways

Endoscopic imaging using optical coherence tomography (OCT) has been demonstrated as clinically useful in the assessment of human airways. These airways have a complex 3D structure, bending, tapering and bifurcating. Previously published 3D OCT reconstructions have not accounted for changes in the orientation and trajectory of the endoscopic probe as it moves through the airway during imaging. We propose a novel endoscopic setup incorporating a magnetic tracking system that accounts for these changes, yielding reconstructions that reveal the true 3D nature of the imaged anatomy. We characterize the accuracy of the system, and present the first published magnetic tracker-assisted endoscopic OCT reconstructions using a phantom airway.

시간영역 광 간섭 단층촬영 시스템의 소형 엔도스코프 제작 및 영상구현

광 간섭 단층촬영 시스템(OCT)을 위한 소형의 광섬유 도관형 주사장치인 엔도스코프(endoscope catheter)를 제작하였다. 깊이방향 주사장치인 원통형 압전소자(PZT)를 이용한 광경로 지연기는 정현파 1 kHz로 구동하여 시간영역에서 엔도스코프 OCT 영상을 구현하였다. 정현파로 구동한 광경로 지연기의 속도는 6 m/s 이고, 깊이방향 스캐닝의 데이터 획득은 3 mm 기준에서 초당 2000 라인이다. 제작한 엔도스코프로 사람의 손가락 및 귀에 대한 초당 10프레임의 OCT 영상을 성공적으로 획득하였다. We fabricated and characterized a compact endoscopic catheter for optical coherence tomography. The optical delay line (ODL), composed of a cylindrical piezoelectric transducer (PZT) and an optical fiber, was operated with a 1 kHz sinusoidal driving wave in the time-domain. When the ODL was driven with a sinusoidal wave function, the axial scanning speed was 6 m/s and the axial acquisition rate was 2000 line/s at a depth of about 3 mm. Endoscopic OCT images of a human finger and earhole were successfully obtained with an image rate of ten frames per second.

Semi-resonant operation of a fiber-cantilever piezotube scanner for stable optical coherence tomography endoscope imaging

A forward-view optical coherence tomography (OCT) scanning catheter has been developed based on a fiber-cantilever piezotube scanner by using a semi-resonant scan strategy for a better scan performance. A compact endoscope catheter was fabricated by using a tubular piezoelectric actuator with quartered electrodes in combination with a resonant fiber cantilever. A cantilever weight was attached to the fiber cantilever to reduce the resonance frequency down to 63 Hz, well in the desirable range for Fourier-domain OCT. The resonant-cantilever scanner was driven at semi-resonance frequencies that were well out of the resonance peak but within a range of partial resonance. This driving strategy has been found to minimize the phase difference between the two scan axes for a better scan stability against environmental perturbations as well as for a driving simplicity. By driving the two axes at slightly different frequencies, a low-order Lissajous pattern has been obtained for a 2D area scan. 3D OCT images have been successfully acquired in an acquisition time of 1.56 seconds for a tomogram volume of 2.2 × 2.2 × 2.1 mm3. They were reconstructed without any scan calibration by extracting the scan timing from the image data. In addition, it has been found that the Lissajous scan strategy provides a means to compensate the relative axial motion of a sample for a correct imaged morphology.

Image analysis for classification of dysplasia in Barrett’s esophagus using endoscopic optical coherence tomography

Barrett’s esophagus (BE) and associated adenocarcinoma have emerged as a major health care problem. Endoscopic optical coherence tomography is a microscopic sub-surface imaging technology that has been shown to differentiate tissue layers of the gastrointestinal wall and identify dysplasia in the mucosa, and is proposed as a surveillance tool to aid in management of BE. In this work a computer-aided diagnosis (CAD) system has been demonstrated for classification of dysplasia in Barrett’s esophagus using EOCT. The system is composed of four modules: region of interest segmentation, dysplasia-related image feature extraction, feature selection, and site classification and validation. Multiple feature extraction and classification methods were evaluated and the process of developing the CAD system is described in detail. Use of multiple EOCT images to classify a single site was also investigated. A total of 96 EOCT image-biopsy pairs (63 non-dysplastic, 26 low-grade and 7 high-grade dysplastic biopsy sites) from a previously described clinical study were analyzed using the CAD system, yielding an accuracy of 84% for classification of non-dysplastic vs. dysplastic BE tissue. The results motivate continued development of CAD to potentially enable EOCT surveillance of large surface areas of Barrett’s mucosa to identify dysplasia.

Flexible Curled Optical Cord for Bending-Insensitive Optical Imaging Delivery

In the application of optical imaging technologies to the biomedical field, the flexible optical cord is one of the key components used to deliver the reflected optical signal from the internal biological tissue to the biomedical imaging system. However, the conventional optical fibers suffer from a critical wiring limitation, which results in severe power losses under a small bending radius that is less than a few centimeters. In this paper, we demonstrate that holey optical fibers with 18 air holes in cladding have negligible bending loss under a minimum bending radius of 3 mm. Excellent bending insensitivity of the holey fibers can effectively reduce the device size and space, which will be highly beneficial to the flexible endoscopic common-path optical coherence tomography system. A curled optical cord, similar to a curled telephone cord, is specially designed and fabricated to accommodate access of the imaging probe to the biological target at flexible distances. The curled optical cord displays excellent optical properties of a much lower bending loss and better optical imaging quality, but the attenuation and insertion losses are still the same as that of a conventional single-mode fiber-based optical cord.

Quantitative tool for rapid disease mapping using optical coherence tomography images of azoxymethane-treated mouse colon

Optical coherence tomography (OCT) can provide new insight into disease progression and therapy by enabling nondestructive, serial imaging of in vivo cancer models. In previous studies, we have shown the utility of endoscopic OCT for identifying adenomas in the azoxymethane-treated mouse model of colorectal cancer and tracking disease progression over time. Because of improved imaging speed made possible through Fourier domain imaging, three-dimensional imaging of the entire mouse colon is possible. Increased amounts of data can facilitate more accurate classification of tissue but require more time on the part of the researcher to sift through and identify relevant data. We present quantitative software for automatically identifying potentially diseased areas that can be used to create a two-dimensional "disease map" from a three-dimensional Fourier domain OCT data set. In addition to sensing inherent changes in tissue that occur during disease development, the algorithm is sensitive to exogeneous highly scattering gold nanoshells that can be targeted to disease biomarkers. The results of the algorithm were compared to histological diagnosis. The algorithm was then used to assess the ability of gold nanoshells targeted to epidermal growth factor receptor in vivo to enable functional OCT imaging.

Forward-viewing resonant fiber-optic scanning endoscope of appropriate scanning speed for 3D OCT imaging

A forward-viewing resonant fiber-optic endoscope of a scanning speed appropriate for a high-speed Fourier-domain optical coherence tomography (FD-OCT) system was developed to enable real-time, three-dimensional endoscopic OCT imaging. A new method was explored to conveniently tune the scanning frequency of a resonant fiber-optic scanner, by properly selecting the fiber-optic cantilever length, partially changing the mechanical property of the cantilever, and adding a weight to the cantilever tip. Systematic analyses indicated the resonant scanning frequency can be tuned over two orders of magnitude spanning from ~10Hz to ~kHz. Such a flexible scanning frequency range makes it possible to set an appropriate scanning speed of the endoscope to match the different A-scan rates of a variety of FD-OCT systems. A 2.4-mm diameter, 62.5-Hz scanning endoscope appropriate to work with a 40-kHz swept-source OCT (SS-OCT) system was developed and demonstrated for 3D OCT imaging of biological tissues.

T1213 Comparison of Tissue Architectural Changes Between Radiofrequency Ablation and Cryospray Ablation in Barrett's Esophagus Using Endoscopic Three-Dimensional Optical Coherence Tomography

T1213 Comparison of Tissue Architectural Changes Between Radiofrequency Ablation and Cryospray Ablation in Barrett's Esophagus Using Endoscopic Three-Dimensional Optical Coherence Tomography