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ABSTRACT: 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.
Biomedical Optics Express 10/2012; 3(10):2647-57. · 2.33 Impact Factor
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Tsung-Han Tsai,
Chao Zhou,
Yuankai K Tao,
Hsiang-Chieh Lee,
Osman O Ahsen,
Marisa Figueiredo,
Tejas Kirtane, Desmond C Adler,
Joseph M Schmitt,
Qin Huang,
James G Fujimoto,
Hiroshi Mashimo
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ABSTRACT: 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.
Gastrointestinal endoscopy 07/2012; · 6.71 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
World Journal of Gastroenterology 05/2012; 18(20):2502-10. · 2.47 Impact Factor
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Chao Zhou,
Tsung-Han Tsai,
Hsiang-Chieh Lee,
Tejas Kirtane,
Marisa Figueiredo,
Yuankai K Tao,
Osman O Ahsen, Desmond C Adler,
Joseph M Schmitt,
Qin Huang,
James G Fujimoto,
Hiroshi Mashimo
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ABSTRACT: 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.
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.
Cross-sectional study.
Single teaching hospital.
Twenty-six male and 1 female white patients with BE undergoing RFA treatment.
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).
Prevalence, size, and location of buried glands relative to the squamocolumnar junction.
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.
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.
Buried glands were frequently detected with 3D-OCT near the gastroesophageal junction before and after radiofrequency ablation.
Gastrointestinal endoscopy 04/2012; 76(1):32-40. · 6.71 Impact Factor
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Gastrointestinal endoscopy 03/2012; 75(3):675-7; discussion 677. · 6.71 Impact Factor
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Tsung-Han Tsai,
Chao Zhou,
Hsiang-Chieh Lee,
Yuankai K Tao,
Osman O Ahsen,
Marisa Figueiredo, Desmond C Adler,
Joseph M Schmitt,
Qin Huang,
James G Fujimoto,
Hiroshi Mashimo
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ABSTRACT: 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.
Gastroenterology Research and Practice 01/2012; 2012:684832. · 0.98 Impact Factor
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ABSTRACT: 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.
Optics Express 10/2011; 19(21):20930-9. · 3.59 Impact Factor
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ABSTRACT: We demonstrate photothermal optical coherence tomography (OCT) imaging in highly scattering human breast tissue ex vivo. A 120 kHz axial scan rate, swept-source phase-sensitive OCT system at 1300 nm was used to detect phase changes induced by 830 nm photothermal excitation of gold nanoshells. Localized phase modulation was observed 300-600 microm deep in scattering tissue using an excitation power of only 22 mW at modulation frequencies up to 20 kHz. This technique enables integrated structural and molecular-targeted imaging for cancer markers using nanoshells.
Optics Letters 03/2010; 35(5):700-2. · 3.40 Impact Factor
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ABSTRACT: We demonstrate a frequency comb (FC) swept laser and a frequency comb Fourier domain mode locked (FC-FDML) laser for applications in optical coherence tomography (OCT). The fiber-based FC swept lasers operate at a sweep rate of 1kHz and 120kHz, respectively over a 135nm tuning range centered at 1310nm with average output powers of 50mW. A 25GHz free spectral range frequency comb filter in the swept lasers causes the lasers to generate a series of well defined frequency steps. The narrow bandwidth (0.015nm) of the frequency comb filter enables a approximately -1.2dB sensitivity roll off over approximately 3mm range, compared to conventional swept source and FDML lasers which have -10dB and -5dB roll offs, respectively. Measurements at very long ranges are possible with minimal sensitivity loss, however reflections from outside the principal measurement range of 0-3mm appear aliased back into the principal range. In addition, the frequency comb output from the lasers are equally spaced in frequency (linear in k-space). The filtered laser output can be used to self-clock the OCT interference signal sampling, enabling direct fast Fourier transformation of the fringe signals, without the need for fringe recalibration procedures. The design and operation principles of FC swept lasers are discussed and designs for short cavity lasers for OCT and interferometric measurement applications are proposed.
Optics Express 11/2009; 17(23):21257-70. · 3.59 Impact Factor
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ABSTRACT: Three-dimensional (3D) endomicroscopy imaging of the human gastrointestinal tract is demonstrated in vivo using a swept source optical coherence tomography (OCT) system. 3D datasets of normal and pathologic regions of the colon, rectum, and anal verge were obtained from seven volunteers undergoing diagnostic or therapeutic colonoscopy. 3D-OCT enables high resolution endomicroscopy examination through visualization of tissue architectural morphology using virtual cross-sectional images with arbitrary orientations as well as en face projection images. Axial image resolutions of 6 mum in tissue are obtained over a approximately 180 mm2 field with an imaging range of 1.6 mm. A Fourier domain mode locked (FDML) laser providing a tuning range of 180 nm at a sweep rate of 62 kHz is used as the system light source. This clinical pilot study demonstrates the potential of 3D-OCT for distinguishing normal from pathologic colorectal tissue, assessing endoscopic therapies and healing progression.
Optics Express 02/2009; 17(2):784-96. · 3.59 Impact Factor
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ABSTRACT: 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.
Therapeutic Advances in Gastroenterology 01/2009; 2(3):149-156.
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ABSTRACT: We demonstrate en face swept source optical coherence tomography (ss-OCT) without requiring a Fourier transformation step. The electronic optical coherence tomography (OCT) interference signal from a k-space linear Fourier domain mode-locked laser is mixed with an adjustable local oscillator, yielding the analytic reflectance signal from one image depth for each frequency sweep of the laser. Furthermore, a method for arbitrarily shaping the spectral intensity profile of the laser is presented, without requiring the step of numerical apodization. In combination, these two techniques enable sampling of the in-phase and quadrature signal with a slow analog-to-digital converter and allow for real-time display of en face projections even for highest axial scan rates. Image data generated with this technique is compared to en face images extracted from a three-dimensional OCT data set. This technique can allow for real-time visualization of arbitrarily oriented en face planes for the purpose of alignment, registration, or operator-guided survey scans while simultaneously maintaining the full capability of high-speed volumetric ss-OCT functionality.
Optics Letters 12/2008; 33(21):2556-8. · 3.40 Impact Factor
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ABSTRACT: To demonstrate ultrahigh-speed optical coherence tomography (OCT) imaging of the retina and optic nerve head at 249,000 axial scans per second and a wavelength of 1060 nm. To investigate methods for visualization of the retina, choroid, and optic nerve using high-density sampling enabled by improved imaging speed.
A swept-source OCT retinal imaging system operating at a speed of 249,000 axial scans per second was developed. Imaging of the retina, choroid, and optic nerve were performed. Display methods such as speckle reduction, slicing along arbitrary planes, en face visualization of reflectance from specific retinal layers, and image compounding were investigated.
High-definition and three-dimensional (3D) imaging of the normal retina and optic nerve head were performed. Increased light penetration at 1060 nm enabled improved visualization of the choroid, lamina cribrosa, and sclera. OCT fundus images and 3D visualizations were generated with higher pixel density and less motion artifacts than standard spectral/Fourier domain OCT. En face images enabled visualization of the porous structure of the lamina cribrosa, nerve fiber layer, choroid, photoreceptors, RPE, and capillaries of the inner retina.
Ultrahigh-speed OCT imaging of the retina and optic nerve head at 249,000 axial scans per second is possible. The improvement of approximately 5 to 10x in imaging speed over commercial spectral/Fourier domain OCT technology enables higher density raster scan protocols and improved performance of en face visualization methods. The combination of the longer wavelength and ultrahigh imaging speed enables excellent visualization of the choroid, sclera, and lamina cribrosa.
Investigative ophthalmology & visual science 11/2008; 49(11):5103-10. · 3.43 Impact Factor
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ABSTRACT: Optical coherence tomography (OCT) is a rapidly emerging imaging modality that can provide non-invasive, cross-sectional, high-resolution images of tissue morphology in situ and in real-time. In the present series of studies, we used a high-speed OCT imaging system equipped with a frequency-swept laser light source (1.3 mum wavelength) to study living kidneys in situ. Adult, male Munich-Wistar rats were anesthetized, a laparotomy was performed and the living kidneys were exposed for in situ observation. We observed the kidneys prior to, during and following exposure to renal ischemia induced by clamping the renal artery. The effects of intravenous mannitol infusion (1.0 ml of 25%) prior to and during renal ischemia were also studied. Finally, living kidneys were flushed with a renal preservation solution, excised and observed while being stored at 0-4 degrees C. Three-dimensional OCT data sets enabled visualization of the morphology of the uriniferous tubules and the renal corpuscles. When renal ischemia was induced, OCT revealed dramatic shrinkage of tubular lumens due to swelling of the lining epithelium. Three-dimensional visualization and volumetric rendering software provided an accurate evaluation of volumetric changes in tubular lumens in response to renal ischemia. Observations of kidneys flushed with a renal preservation solution and stored at 0-4 degrees C also revealed progressive and significant loss of tubular integrity over time. Intravenous infusion of mannitol solution resulted in thinning of the tubular walls and an increase in the tubular lumen diameters. Mannitol infusion also prevented the cell swelling that otherwise resulted in shrinkage of proximal tubule lumens during ischemia. We conclude that OCT represents an exciting new approach to visualize, in real-time, pathological changes in the living kidney in a non-invasive fashion. Possible clinical applications are discussed.
Laboratory Investigation 05/2008; 88(4):441-9. · 3.64 Impact Factor
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ABSTRACT: The detection of a gold nanoparticle contrast agent is demonstrated using a photothermal modulation technique and phase sensitive optical coherence tomography (OCT). A focused beam from a laser diode at 808 nm is modulated at frequencies of 500 Hz-60 kHz while irradiating a solution containing nanoshells. Because the nanoshells are designed to have a high absorption coefficient at 808 nm, the laser beam induces small-scale localized temperature oscillations at the modulation frequency. These temperature oscillations result in optical path length changes that are detected by a phase-sensitive, swept source OCT system. The OCT system uses a double-buffered Fourier domain mode locked (FDML) laser operating at a center wavelength of 1315 nm and a sweep rate of 240 kHz. High contrast is observed between phantoms containing nanoshells and phantoms without nanoshells. This technique represents a new method for detecting gold nanoparticle contrast agents with excellent signal-to-noise performance at high speeds using OCT.
Optics Express 04/2008; 16(7):4376-93. · 3.59 Impact Factor
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Desmond C Adler,
Jens Stenger,
Iwona Gorczynska,
Henry Lie,
Teri Hensick,
Ron Spronk,
Stephan Wolohojian,
Narayan Khandekar,
James Y Jiang,
Scott Barry,
Alex E Cable,
Robert Huber,
James G Fujimoto
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ABSTRACT: Gold punchwork and underdrawing in Renaissance panel paintings are analyzed using both three-dimensional swept source / Fourier domain optical coherence tomography (3D-OCT) and high resolution digital photography. 3D-OCT can generate en face images with micrometer-scale resolutions at arbitrary sectioning depths, rejecting out-of-plane light by coherence gating. Therefore 3D-OCT is well suited for analyzing artwork where a surface layer obscures details of interest. 3D-OCT also enables cross-sectional imaging and quantitative measurement of 3D features such as punch depth, which is beneficial for analyzing the tools and techniques used to create works of art. High volumetric imaging speeds are enabled by the use of a Fourier domain mode locked (FDML) laser as the 3D-OCT light source. High resolution infrared (IR) digital photography is shown to be particularly useful for the analysis of underdrawing, where the materials used for the underdrawing and paint layers have significantly different IR absrption properties. In general, 3D-OCT provides a more flexible and comprehensive analysis of artwork than high resolution photography, but also requires more complex instrumentation and data analysis.
Optics Express 12/2007; 15(24):15972-86. · 3.59 Impact Factor
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ABSTRACT: Swept source optical coherence microscopy (OCM) enables cellular resolution en face imaging as well as integration with optical coherence tomography (OCT) cross sectional imaging. A buffered Fourier domain mode-locked (FDML) laser light source provides high speed, three dimensional imaging. Image resolutions of 1.6 microm x 8 microm (transverse x axial) with a 220 microm x 220 microm field of view and sensitivity higher than 98 dB are achieved. Three dimensional cellular imaging is demonstrated in vivo in the Xenopus laevis tadpole and ex vivo in the rat kidney and human colon.
Optics Express 06/2007; 15(10):6210-7. · 3.59 Impact Factor
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ABSTRACT: Buffered Fourier domain mode-locked (FDML) lasers are demonstrated for dynamic phase-sensitive optical coherence tomography (OCT) and 3D OCT phase microscopy. Systems are operated at sweep speeds of 42, 117, and 370 kHz, and displacement sensitivities of 39, 52, and 102 pm are achieved, respectively. Sensitivities are comparable to spectrometer-based OCT phase microscopy systems, but much faster acquisition speeds are possible. An additional factor of sqrt 2 improvement in noise performance is observed for differential phase measurements, which is important for Doppler OCT. Dynamic measurements of piezoelectric transducer motion and static 3D OCT phase microscopy are demonstrated. Buffered FDML lasers provide excellent displacement sensitivities at extremely high sweep speeds.
Optics Letters 04/2007; 32(6):626-8. · 3.40 Impact Factor
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ABSTRACT: We describe buffered Fourier domain mode locking (FDML), a technique for tailoring the output and multiplying the sweep rate of FDML lasers. Buffered FDML can be used to create unidirectional wavelength sweeps from the normal bidirectional sweeps in an FDML laser without sacrificing sweep rate. We also investigate the role of the laser source in dynamic range versus sensitivity performance in optical coherence tomography (OCT) imaging. Unidirectional sweep rates of 370 kHz over a 100 nm range at a center wavelength of 1300 nm are achieved. High-speed, swept-source OCT is demonstrated at record speeds of up to 370,000 axial scans per second.
Optics Letters 11/2006; 31(20):2975-7. · 3.40 Impact Factor
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ABSTRACT: A spatially adaptive two-dimensional wavelet filter is used to reduce speckle noise in time-domain and Fourier-domain optical coherence tomography (OCT) images. Edges can be separated from discontinuities that are due to noise, and noise power can be attenuated in the wavelet domain without significantly compromising image sharpness. A single parameter controls the degree of noise reduction. When this filter is applied to ophthalmic OCT images, signal-to-noise ratio improvements of >7 dB are attained, with a sharpness reduction of <3%.
Optics Letters 12/2004; 29(24):2878-80. · 3.40 Impact Factor
