Desmond C. Adler

Buffered Fourier domain mode locking: Unidirectional swept laser sources for optical coherence tomography imaging at 370,000 lines/s.

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.

Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head.

PURPOSE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Fourier domain mode locking at 1050 nm for ultra-high-speed optical coherence tomography of the human retina at 236,000 axial scans per second.

A Fourier domain mode-locked (FDML) laser at 1050 nm for ultra-high-speed optical coherence tomography (OCT) imaging of the human retina is demonstrated. Achievable performance, physical limitations, design rules, and scaling principles for FDML operation and component choice in this wavelength range are discussed. The fiber-based FDML laser operates at a sweep rate of 236 kHz over a 63 nm tuning range, with 7 mW average output power. Ultra-high-speed retinal imaging is demonstrated at 236,000 axial scans per second. This represents a speed improvement of approximately10x over typical high-speed OCT systems, paving the way for densely sampled volumetric data sets and new imaging protocols.

Speckle reduction in optical coherence tomography images by use of a spatially adaptive wavelet filter

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%.

Photothermal detection of gold nanoparticles using phase-sensitive optical coherence tomography

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.

Phase-sensitive optical coherence tomography at up to 370,000 lines per second using buffered Fourier domain mode-locked lasers.

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.

Ultrahigh-speed optical coherence tomography imaging and visualization of the embryonic avian heart using a buffered Fourier Domain Mode Locked laser

The embryonic avian heart is an important model for studying cardiac developmental biology. The mechanisms that govern the development of a four-chambered heart from a peristaltic heart tube are largely unknown due in part to a lack of adequate imaging technology. Due to the small size and rapid motion of the living embryonic avian heart, an imaging system with high spatial and temporal resolution is required to study these models. Here, an optical coherence tomography (OCT) system using a buffered Fourier Domain Mode Locked (FDML) laser is applied for ultrahigh-speed non-invasive imaging of embryonic quail hearts at 100,000 axial scans per second. The high scan rate enables the acquisition of high temporal resolution 2D datasets (195 frames per second or 5.12 ms between frames) and 3D datasets (10 volumes per second). Spatio-temporal details of cardiac motion not resolvable using previous OCT technology are analyzed. Visualization and measurement techniques are developed to non-invasively observe and quantify cardiac motion throughout the brief period of systole (less than 50 msec) and diastole. This marks the first time that the preseptated embryonic avian heart has been imaged in 4D without the aid of gating and the first time it has been viewed in cross section during looping with extremely high temporal resolution, enabling the observation of morphological dynamics of the beating heart during systole.

Ultrahigh resolution optical coherence tomography imaging with a broadband superluminescent diode light source

Ultrahigh resolution optical coherence tomography imaging is performed with a compact broadband superluminescent diode light source. The source consists of two multiplexed broadband superluminescent diodes and has a power output of 4 mW with a spectral bandwidth of 155 nm, centered at a wavelength of 890 nm. In vivo imaging was performed with approximately 2.3 microm axial resolution in scattering tissue and approximately 3.2 microm axial resolution in the retina. These results demonstrate that it is possible to perform in vivo ultrahigh resolution optical coherence tomography imaging using a superluminescent diode light source that is inexpensive, compact, and easy to operate.

Three-dimensional endomicroscopy of the human colon using optical coherence tomography

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.

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 Barretts 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.