Structural markers observed with endoscopic 3-dimensional optical coherence tomography correlating with Barrett's esophagus radiofrequency ablation treatment response (with videos).

BACKGROUND: Radiofrequency ablation (RFA) is effective for treating Barrett's esophagus (BE) but often involves multiple endoscopy sessions over several months to achieve complete response. OBJECTIVE: Identify structural markers that correlate with treatment response by using 3-dimensional (3-D) optical coherence tomography (OCT; 3-D OCT). DESIGN: Cross-sectional. SETTING: Single teaching hospital. PATIENTS: Thirty-three patients, 32 male and 1 female, with short-segment (<3 cm) BE undergoing RFA treatment. INTERVENTION: Patients were treated with focal RFA, and 3-D OCT was performed at the gastroesophageal junction before and immediately after the RFA treatment. Patients were re-examined with standard endoscopy 6 to 8 weeks later and had biopsies to rule out BE if not visibly evident. MAIN OUTCOME MEASUREMENTS: The thickness of BE epithelium before RFA and the presence of residual gland-like structures immediately after RFA were determined by using 3-D OCT. The presence of BE at follow-up was assessed endoscopically. RESULTS: BE mucosa was significantly thinner in patients who achieved complete eradication of intestinal metaplasia than in patients who did not achieve complete eradication of intestinal metaplasia at follow-up (257 ± 60 µm vs 403 ± 86 µm; P < .0001). A threshold thickness of 333 µm derived from receiver operating characteristic curves corresponded to a 92.3% sensitivity, 85% specificity, and 87.9% accuracy in predicting the presence of BE at follow-up. The presence of OCT-visible glands immediately after RFA also correlated with the presence of residual BE at follow-up (83.3% sensitivity, 95% specificity, 90.6% accuracy). LIMITATIONS: Single center, cross-sectional study in which only patients with short-segment BE were examined. CONCLUSION: Three-dimensional OCT assessment of BE thickness and residual glands during RFA sessions correlated with treatment response. Three-dimensional OCT may predict responses to RFA or aid in making real-time RFA retreatment decisions in the future.

Characterization of buried glands before and after radiofrequency ablation by using 3-dimensional optical coherence tomography (with videos).

BACKGROUND: Radiofrequency ablation (RFA) is an endoscopic technique used to eradicate Barrett's esophagus (BE). However, such ablation can commonly lead to neosquamous epithelium overlying residual BE glands not visible by conventional endoscopy and may evade detection on random biopsy samples. OBJECTIVE: To demonstrate the capability of endoscopic 3-dimensional optical coherence tomography (3D-OCT) for the identification and characterization of buried glands before and after RFA therapy. DESIGN: Cross-sectional study. SETTING: Single teaching hospital. PATIENTS: Twenty-six male and 1 female white patients with BE undergoing RFA treatment. INTERVENTIONS: 3D-OCT was performed at the gastroesophageal junction in 18 patients before attaining complete eradication of intestinal metaplasia (pre-CE-IM group) and in 16 patients after CE-IM (post-CE-IM group). MAIN OUTCOME MEASUREMENTS: Prevalence, size, and location of buried glands relative to the squamocolumnar junction. RESULTS: 3D-OCT provided an approximately 30 to 60 times larger field of view compared with jumbo and standard biopsy and sufficient imaging depth for detecting buried glands. Based on 3D-OCT results, buried glands were found in 72% of patients (13/18) in the pre-CE-IM group and 63% of patients (10/16) in the post-CE-IM group. The number (mean [standard deviation]) of buried glands per patient in the post-CE-IM group (7.1 [9.3]) was significantly lower compared with the pre-CE-IM group (34.4 [44.6]; P = .02). The buried gland size (P = .69) and distribution (P = .54) were not significantly different before and after CE-IM. LIMITATIONS: A single-center, cross-sectional study comparing patients at different time points in treatment. Lack of 1-to-1 coregistered histology for all OCT data sets obtained in vivo. CONCLUSION: Buried glands were frequently detected with 3D-OCT near the gastroesophageal junction before and after radiofrequency ablation.

Extended coherence length Fourier domain mode locked lasers at 1310 nm.

Fourier domain mode locked (FDML) lasers are excellent tunable laser sources for frequency domain optical coherence tomography (FD-OCT) systems due to their combination of high sweep rates, large tuning ranges, and high output powers. However, conventional FDML lasers provide coherence lengths of only 4-10 mm, limiting their use in demanding applications such as intravascular OCT where coherence lengths of >20 mm are required for optimal imaging of large blood vessels. Furthermore, like most swept lasers, conventional FDML lasers produce only one useable sweep direction per tunable filter drive cycle, halving the effective sweep rate of the laser compared to the filter drive frequency. Here, we demonstrate a new class of FDML laser incorporating broadband dispersion compensation near 1310 nm. Elimination of chromatic dispersion in the FDML cavity results in the generation of forward (short to long wavelength) and backward (long to short wavelength) sweeps with substantially identical properties and coherence lengths of >21 mm. This advance enables long-range, high-speed FD-OCT imaging without the need for optical buffering stages, significantly reducing laser cost and complexity.

Effects of axial resolution improvement on optical coherence tomography (OCT) imaging of gastrointestinal tissues.

Optical coherence tomography (OCT) is an emerging medical imaging technology which generates high resolution, cross-sectional images in situ, without the need for excisional biopsy. Previous clinical studies using endoscopic OCT with standard 10-15 microm axial resolution have demonstrated its capability in diagnosing Barrett's esophagus (BE) and high-grade dysplasia (HGD). Quantitative OCT image analysis has shown promise for detecting HGD in Barrett's esophagus patients. We recently developed an endoscopic OCT system with an improved axial resolution of approximately 5 microm. The goal in this manuscript is to compare standard resolution OCT and ultrahigh resolution OCT (UHR-OCT) for image quality and computer-aided detection using normal and Barrett's esophagus. OCT images of gastrointestinal (GI) tissues were obtained using UHR-OCT (5.5 microm) and standard resolution OCT (13 microm). Image quality including the speckle size and sharpness was compared. Texture features of endoscopic OCT images from normal and Barrett's esophagus were extracted using quantitative metrics including spatial frequency analysis and statistical texture analysis. These features were analyzed using principal component analysis (PCA) to reduce the vector dimension and increase the discriminative power, followed by linear discrimination analysis (LDA). UHR-OCT images of GI tissues improved visualization of fine architectural features compared to standard resolution OCT. In addition, the quantitative image feature analysis showed enhanced discrimination of normal and Barrett's esophagus with UHR-OCT. The ability of UHR-OCT to resolve tissue morphology at improved resolution enables visualization of subtle features in OCT images, which may be useful in disease diagnosis. Enhanced classification of image features using UHR-OCT promises to help in the computer-aided diagnosis of GI diseases.

Characterization of atherosclerosis plaques by measuring both backscattering and attenuation coefficients in optical coherence tomography.

Intravascular optical coherence tomography (OCT) has been proven a powerful diagnostic tool for cardiovascular diseases. However, the optical mechanism for the qualitative observations are still absent. We address the fundamental issues that underlie the tissue characterization of OCT images obtained from coronary arteries. For this, we investigate both the attenuation and the backscattering properties of different plaque components of postmortem human cadaver coronary arteries. The artery samples are examined both from lumen surface using a catheter and from transversely cut surface using an OCT microscope, where OCT images could be matched to histology exactly. Light backscattering coefficient microb and attenuation coefficients microt are determined for three basic plaque types based on a single-scattering physical model: calcification (microb=4.9+/-1.5 mm(-1), microt=5.7+/-1.4 mm(-1)), fibers (microb=18.4+/-6.4 mm(-1), microt=6.4+/-1.2 mm(-1)), and lipid pool (microb=28.1+/-8.9 mm(-1), microt=13.7+/-4.5 mm(-1)). Our results not only explain the origins of many qualitative OCT features, but also show that combination of backscattering and attenuation coefficient measurements can be used for contrast enhancing and better tissue characterization.

High-resolution three-dimensional optical coherence tomography imaging of kidney microanatomy ex vivo.

Optical coherence tomography (OCT) is an emerging medical imaging technology that enables high-resolution, noninvasive, cross-sectional imaging of microstructure in biological tissues in situ and in real time. When combined with small-diameter catheters or needle probes, OCT offers a practical tool for the minimally invasive imaging of living tissue morphology. We evaluate the ability of OCT to image normal kidneys and discriminate pathological changes in kidney structure. Both control and experimental preserved rat kidneys were examined ex vivo by using a high-resolution OCT imaging system equipped with a laser light source at 1.3-microm wavelength. This system has a resolution of 3.3 microm (depth) by 6 microm (transverse). OCT imaging produced cross-sectional and en face images that revealed the sizes and shapes of the uriniferous tubules and renal corpuscles. OCT data revealed significant changes in the uriniferous tubules of kidneys preserved following an ischemic or toxic (i.e., mercuric chloride) insult. OCT data was also rendered to produce informative three-dimensional (3-D) images of uriniferous tubules and renal corpuscles. The foregoing observations suggest that OCT can be a useful non-excisional, real-time modality for imaging pathological changes in donor kidney morphology prior to transplantation.

Thinking inside the graft: applications of optical coherence tomography in coronary artery bypass grafting.

Recent advances in catheter-based optical coherence tomography (OCT) have provided the necessary resolution and acquisition speed for high-quality intravascular imaging. Complications associated with clearing blood from the vessel of a living patient have prevented its wider acceptance. We identify a surgical application that takes advantage of the vascular imaging powers of OCT but that circumvents the difficulties. Coronary artery bypass grafting (CABG) is the most commonly performed major surgery in America. A critical determinant of its outcome has been postulated to be injury to the conduit vessel incurred during the harvesting procedure or pathology preexistent in the harvested vessel. As a test of feasibility, intravascular OCT imaging is obtained from the radial arteries (RAs) and/or saphenous veins (SVs) of 35 patients scheduled for CABG. Pathologies detected by OCT are compared to registered histological sections obtained from discarded segments of each graft. OCT reliably detects atherosclerotic lesions in the RAs and discerns plaque morphology as fibrous, fibrocalcific, or fibroatheromatous. OCT is also used to assess intimal trauma and residual thrombi related to endoscopic harvest and the quality of the distal anastomosis. We demonstrate the feasibility of OCT imaging as an intraoperative tool to select conduit vessels for CABG.

Optical coherence tomography for the characterization of basal cell carcinoma in vivo: a pilot study.

BACKGROUND: Optical coherence tomography combines principles of ultrasonography and optical interferometry to provide real-time cross-sectional images of subsurface microstructure of tissue in vivo. OBJECTIVE: The purpose of this pilot study was to define and characterize basal cell carcinoma by using optical coherence tomography. METHODS: Twenty-three patients with 49 lesions clinically suggestive of superficial basal cell carcinoma were recruited. Optical coherence tomography was used to characterize the features of the pearly papules in real time and in vivo. Shave biopsy and light microscopic images were compared with images from optical coherence tomography. RESULTS: Basal cell carcinoma was identified in 27 patients; all 27 had optical coherence tomographic images for comparison. Seven images were uninterpretable, probably because of technical problems. Of the remainder, 20 sites matched the histologic features seen on light microscopy, with excellent correlation between optical coherence tomographic images and histopathologic features of superficial, nodular, micronodular and infiltrative basal cell carcinomas. LIMITATIONS: This study was limited by the small number of patients examined. Also, as this study was not designed as an intent-to-diagnose study, the actual predictive value of optical coherence tomography technology remains unproven. CONCLUSIONS: Optical coherence tomography technology has potential for the diagnosis and histopathologic characterization of basal cell cancer. Additional studies to determine any practical role for optical coherence tomography are indicated.

Optical coherence tomography in the diagnosis and treatment of neurological disorders.

Optical contrast is often the limiting factor in the imaging of live biological tissue. Studies were conducted in postmortem human brain to identify clinical applications where the structures of interest possess high intrinsic optical contrast and where the real-time, high-resolution imaging capabilities of optical coherence tomography (OCT) may be critical. Myelinated fiber tracts and blood vessels are two structures with high optical contrast. The ability to image these two structures in real time may improve the efficacy and safety of a neurosurgical procedure to treat Parkinson's disease called deep brain stimulation (DBS). OCT was evaluated as a potential optical guidance system for DBS in 25 human brains. The results suggest that catheter-based OCT has the resolution and contrast necessary for DBS targeting. The results also demonstrate the ability of OCT to detect blood vessels with high sensitivity, suggesting a possible means to avoid their laceration during DBS. Other microscopic structures in the human brain with high optical contrast are pathological vacuoles associated with transmissible spongiform encephalopathy (TSE). TSE include diseases such as Mad Cow disease and Creutzfeldt-Jakob disease (CJD) in humans. OCT performed on the brain from a woman who died of CJD was able to detect clearly the pathological vacuoles.

Volumetric assessment of lesion severity with optical coherence tomography: relationship with fractional flow.

AIMS: Frequency-domain optical coherence tomography (FD-OCT) provides a rapid tomographic scan of a coronary vessel, with an accurate reconstruction of its lumen profile. An FD-OCT-based metric that corresponds more closely with physiological significance of lesions may enable more precise guidance of interventional procedures. The aim of this feasibility study was to evaluate a new method for quantifying coronary lesion severity that estimates hyperaemic flow resistance of branched vessel segments imaged by FD-OCT. METHODS AND RESULTS: An analytical flow model was developed that relates fractional flow reserve (FFR) to the vascular resistance ratio (VRR), a measure of blood flow resistance derived from volumetric FD-OCT lumen profiles. The VRR-FFR relationship was evaluated in 21 patients on whom both pressure measurement and FD-OCT imaging were performed in a random order during maximal hyperaemia. Lesion severity assessed by VRR showed a stronger linear correlation with FFR measurements (before model optimisation [blinded]: r=0.81; p<0.001; root mean square error [RMSE]=0.095 FFR units; after model optimisation [unblinded]: r=0.91; p<0.001; RMSE=0.066 FFR units) than quantitative coronary angiography and FD-OCT-derived measurements of minimum lumen area (r=0.67; p=0.0012) and per cent area stenosis (r=-0.61; p=0.004). CONCLUSIONS: Accurate volumetric measurement of the lumen profile with FD-OCT correlates more closely with FFR than standard metrics derived from single image cross-sections. VRR shows promise as a method for evaluating lesion severity.

Extended coherence length megahertz FDML and its application for anterior segment imaging.

We present a 1300 nm Fourier domain mode locked (FDML) laser for optical coherence tomography (OCT) that combines both, a high 1.6 MHz wavelength sweep rate and an ultra-long instantaneous coherence length for rapid volumetric deep field imaging. By reducing the dispersion in the fiber delay line of the FDML laser, the instantaneous coherence length and hence the available imaging range is approximately quadrupled compared to previously published MHz-FDML setups, the imaging speed is increased by a factor of 16 compared to previous extended coherence length results. We present a detailed characterization of the FDML laser performance. We demonstrate for the first time MHz-OCT imaging of the anterior segment of the human eye. The OCT system provides enough imaging depth to cover the whole range from the top surface of the cornea down to the crystalline lens.

Cervical inlet patch-optical coherence tomography imaging and clinical significance.

AIM: To demonstrate the feasibility of optical coherence tomography (OCT) imaging in differentiating cervical inlet patch (CIP) from normal esophagus, Barrett's esophagus (BE), normal stomach and duodenum. METHODS: This study was conducted at the Veterans Affairs Boston Healthcare System (VABHS). Patients undergoing standard esophagogastroduodenoscopy at VABHS, including one patient with CIP, one representative patient with BE and three representative normal subjects were included. White light video endoscopy was performed and endoscopic 3D-OCT images were obtained in each patient using a prototype OCT system. The OCT imaging probe passes through the working channel of the endoscope to enable simultaneous video endoscopy and 3D-OCT examination of the human gastrointestinal (GI) tract. Standard hematoxylin and eosin (H and E) histology was performed on biopsy or endoscopic mucosal resection specimens in order to compare and validate the 3D-OCT data. RESULTS: CIP was observed from a 68-year old male with gastroesophageal reflux disease. The CIP region appeared as a pink circular lesion in the upper esophagus under white light endoscopy. OCT imaging over the CIP region showed columnar epithelium structure, which clearly contrasted the squamous epithelium structure from adjacent normal esophagus. 3D-OCT images obtained from other representative patients demonstrated distinctive patterns of the normal esophagus, BE, normal stomach, and normal duodenum bulb. Microstructures, such as squamous epithelium, lamina propria, muscularis mucosa, muscularis propria, esophageal glands, Barrett's glands, gastric mucosa, gastric glands, and intestinal mucosal villi were clearly observed with OCT and matched with H and E histology. These results demonstrated the feasibility of using OCT to evaluate GI tissue morphology in situ and in real-time. CONCLUSION: We demonstrate in situ evaluation of CIP microstructures using 3D-OCT, which may be a useful tool for future diagnosis and follow-up of patients with CIP.

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.

Automatic detection of stent struts with thick neointimal growth in intravascular optical coherence tomography image sequences.

To assist cardiologists investigating neointimal tissue growth on stents during follow-up with optical coherence tomography (OCT), we developed an automatic algorithm to locate deeply buried stent struts and to quantify the restenosis burden. The technique is based on an improved steerable filter for computing the local ridge strength and orientation. It also uses an ellipsoid fitting algorithm and continuity criteria to obtain globally optimal stent localization. The restenosis burden calculations were compared to manual assessment of OCT coronary artery image data obtained from in vivo human clinical studies. Compared to manual assessment by expert readers, the algorithm operated with > 97% accuracy in the measurement of mean and maximum restenosis burden. The results indicated that the technique yielded comparable accuracy in measuring restenosis burden, and significantly reduced user interaction time.

Semiautomatic segmentation and quantification of calcified plaques in intracoronary optical coherence tomography images.

Coronary calcified plaque (CP) is both an important marker of atherosclerosis and major determinant of the success of coronary stenting. Intracoronary optical coherence tomography (OCT) with high spatial resolution can provide detailed volumetric characterization of CP. We present a semiautomatic method for segmentation and quantification of CP in OCT images. Following segmentation of the lumen, guide wire, and arterial wall, the CP was localized by edge detection and traced using a combined intensity and gradient-based level-set model. From the segmentation regions, quantification of the depth, area, angle fill fraction, and thickness of the CP was demonstrated. Validation by comparing the automatic results to expert manual segmentation of 106 in vivo images from eight patients showed an accuracy of 78±9%. For a variety of CP measurements, the bias was insignificant (except for depth measurement) and the agreement was adequate when the CP has a clear outer border and no guide-wire overlap. These results suggest that the proposed method can be used for automated CP analysis in OCT, thereby facilitating our understanding of coronary artery calcification in the process of atherosclerosis and helping guide complex interventional strategies in coronary arteries with superficial calcification.

Current and future developments in intracoronary optical coherence tomography imaging.

Optical coherence tomography (OCT) has become a key intracoronary imaging modality able to traverse some of the limitations of angiography and intravascular ultrasound. In vivo imaging with high resolution (around 15 micrometres) has given unique insights into not only atherosclerotic plaque, but also to the understanding of tissue responses underlying stent implantation. Novel developments with faster OCT pullback speeds will further simplify the procedural requirements and eventually eliminate the need for proximal vessel balloon occlusion during image acquisition. This report explores the current and future developments in OCT technology that will see this unique imaging modality become a key player in both the clinical and research arena for the interventional cardiologist.

Effective treatment of chronic radiation proctitis using radiofrequency ablation.

Endoscopic argon plasma coagulation and bipolar electrocautery are currently preferred treatments for chronic radiation proctitis, but ulcerations and strictures frequently occur. Radiofrequency ablation (RFA) has been successful for mucosal ablation in the esophagus. Here we report the efficacy of RFA with the BarRx Halo(90) system in three patients with bleeding from chronic radiation proctitis. In all cases, the procedure was well tolerated and hemostasis was achieved after 1 or 2 RFA sessions. Re-epithelialization of squamous mucosa was observed over areas of prior hemorrhage. No stricturing or ulceration was seen on follow-up up to 19 months after RFA treatment. Real-time endoscopic optical coherence tomography (EOCT) visualized epithelialization and subsurface tissue microvasculature pre- and post-treatment, demonstrating its potential for follow-up assessment of endoscopic therapies.

Correlation of thickness of basal cell carcinoma by optical coherence tomography in vivo and routine histologic findings: a pilot study.

BACKGROUND: Optical coherence tomography uses advanced photonics and fiber optics to obtain high-resolution cross-sectional images and tissue characterization in real time. OBJECTIVE: The objective was to correlate measurements of the depth of basal cell carcinomas obtained by optical coherence tomography and standard histopathologic examinations. METHODS: Twenty previously scanned optical coherence tomography images of histopathologically confirmed basal cell carcinoma were reviewed. A computer-generated depth scale was used to measure the depth of the neoplasm. These measurements were compared with direct measurements of tumor thickness of analogous tissue specimens made with a microscope micrometer. RESULTS: All 20 sites demonstrated excellent correlation of tissue thickness, to a depth of about 1 mm, estimated by optical coherence tomography or routine histopathologic tests. This depth correlation was consistent across several different types of basal cell carcinoma observed. CONCLUSION: Optical coherence tomography, compared with routine histopathologic techniques, shows promise as a method for estimating the superficial thickness of basal cell carcinoma.