Significance: Corneal cross-linking (CXL) is a well-known procedure for treating certain eye disorders such as keratoconus. However, characterization of the biomechanical changes in the cornea as a result of this procedure is still under active research. Specifically, there is a clinical need for high-resolution characterization of individual corneal layers.
Aim: A high-resolution elastography method in conjunction with a custom optical coherence tomography system is used to track these biomechanical changes in individual corneal layers. Pre- and post-treatment analysis for both low-dose and high-dose CXL experiments are performed.
Approach: A recently developed elastography technique that utilizes the theory of reverberant shear wave fields, with optical coherence tomography as the modality, is applied to pig corneas ex vivo to evaluate elasticity changes associated with corneal CXL. Sets of low-dose and high-dose CXL treatments are evaluated before and after treatments with three pairs of pig corneas per experiment.
Results: The reverberant three-dimensional (3D) optical coherence elastography (OCE) technique can identify increases in elasticity associated with both low-dose and high-dose CXL treatments. There is a notable graphical difference between low-dose and high-dose treatments. In addition, the technique is able to identify which layers of the cornea are potentially affected by the CXL procedure and provides insight into the nonlinearity of the elasticity changes.
Conclusions: The reverberant 3D OCE technique can identify depth-resolved changes in elasticity of the cornea associated with CXL procedures. This method could be translated to assess and monitor CXL efficacy in various clinical settings.
Fourier domain mode locked (FDML) lasers provide high sweep rates, broad tuning ranges, and high output powers for
optical coherence tomography (OCT) systems. However, presently-known FDML lasers at 1300 nm have relatively
short coherence lengths, limiting the size of samples that can be imaged. Furthermore, FDML lasers produce only one
useable sweep direction. We report FDML coherence length extension by incorporating advanced dispersion
compensation modules (DCMs). DCMs eliminate group velocity dispersion in the cavity, doubling coherence lengths
and ensuring uniform axial resolution over the imaging range. Additionally, forward and backward sweeps are nearly
identical, removing the need for external buffering stages.
We report clinical study results of three-dimensional (3D) in vivo imaging of human coronary arteries using frequency domain optical coherence tomography (FD-OCT). At the time of this report, over 2000 patients in over 10 countries have been imaged using FD-OCT systems and disposable fiberoptic catheters developed by LightLab Imaging Inc. The first commercial versions of the systems were introduced in Europe in May 2009. The system operates at 50,000 axial lines/s, performing a 50 mm spiral pullback in 2.5 seconds with a rotational frame rate of 100 Hz. The commercial system employs a proprietary micro-cavity swept laser, allowing imaging of vessel diameters up to 10 mm. Data compiled from early studies indicate that FD-OCT is being used for post-intervention imaging of deployed coronary stents in over 40% of cases. High-resolution 3D imaging of stent geometry immediately following deployment enables
detection of stent malapposition, which can increase the risk of thrombosis. Longer term follow-up imaging of stented vessels can detect thrombus formation, which can be treated pharmacologically, and excessive neointimal growth, which may require angioplasty or re-stenting. FD-OCT is also being used for pre-intervention imaging of stenotic lesions in about 60% of cases. Here FD-OCT is used to measure the minimum lumen area and to identify calcified deposits, side branches, or other vascular structures that could interfere with the stenting procedure. Overall, FD-OCT continues to be
adopted at an increasing rate and has provided interventional cardiologists with a powerful tool for pre- and postintervention
assessment of the coronary arteries.
Barrett's esophagus (BE) with high-grade dysplasia is generally treated by endoscopic mucosal resection or
esophagectomy. Radiofrequency ablation (RFA) is a recent treatment that allows broad and superficial
ablation for BE. Endoscopic three-dimensional optical coherence tomography (3D-OCT) is a volumetric
imaging technique that is uniquely suited for follow-up surveillance of RFA treatment. 3D-OCT uses a thin
fiberoptic imaging catheter placed down the working channel of a conventional endoscope. 3D-OCT enables
en face and cross-sectional evaluation of the esophagus for detection of residual BE, neo-squamous mucosa,
or buried BE glands. Patients who had undergone RFA treatment with the BARRX HALO90 system were
recruited and imaged with endoscopic 3D-OCT before and after (3-25 months) RFA treatment. 3D-OCT
findings were compared to pinch biopsy to confirm the presence or absence of squamous epithelium or buried
BE glands following RFA. Gastric, BE, and squamous epithelium were readily distinguished from 3D-OCT
over a large volumetric field of view (8mmx20mmx1.6 mm) with ~5μm axial resolution. In all patients, neosquamous
epithelium (NSE) was observed in regions previously treated with RFA. A small number of
isolated glands were found buried beneath the regenerated NSE and lamina propria. NSE is a marker of
successful ablative therapy, while buried glands may have malignant potential and are difficult to detect using
conventional video endoscopy and random biopsy. Buried glands were not observed with pinch biopsy due to
their extremely sparse distribution. These results indicate a potential benefit of endoscopic 3D-OCT for
follow-up assessment of ablative treatments for BE.
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 cavity of 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 ~-1.2dB
sensitivity roll off over ~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 interferometric measurement applications are proposed.
We report on the design of a frequency domain optical coherence tomography (FD-OCT) system, fiber optic imaging
catheter, and image processing algorithms for in vivo clinical use in the human coronary arteries. This technology
represents the third generation of commercially-available OCT system developed at LightLab Imaging Inc. over the last
ten years, enabling three-dimensional (3D) intravascular imaging at unprecedented speeds and resolutions for a
commercial system. The FD-OCT engine is designed around an exclusively licensed micro-cavity swept laser that was
co-developed with AXSUN Technologies Ltd. The laser's unique combination of high sweep rates, broad tuning ranges,
and narrow linewidth enable imaging at 50,000 axial lines/s with an axial resolution of < 16 μm in tissue. The disposable
2.7 French (0.9 mm) imaging catheter provides a spot size of < 30 μm at a working distance of 2 mm. The catheter is
rotated at 100 Hz and pulled back 50 mm at 20 mm/s to conduct a high-density spiral scan in 2.5 s. Image processing
algorithms have been developed to provide clinically important measurements of vessel lumen dimensions, stent
malapposition, and neointimal thickness. This system has been used in over 2000 procedures since August 2007 at over
40 clinical sites, providing cardiologists with an advanced tool for 3D assessment of the coronary arteries.
KEYWORDS: Optical coherence tomography, Data acquisition, Imaging systems, Colon, In vivo imaging, Endomicroscopy, 3D acquisition, Tissues, 3D image processing, Endoscopy
We report an endoscopic optical coherence tomography (OCT) system based on a Fourier Domain Mode Locked
(FDML) laser, a novel data acquisition (DAQ) system with optical frequency clocking, and a high-speed spiralscanning
fiber probe. The system is capable of acquiring three-dimensional (3D) in vivo datasets at 100,000 axial
lines/s and 50 frames/s, enabled by the high sweep rates of the FDML laser and the efficient data processing of
the DAQ system. This high imaging rate allows densely-sampled 3D datasets to be acquired, giving a resolvable
feature size of 9 &mgr;m x 20 &mgr;m x 7 &mgr;m (transverse x longitudinal x axial, XYZ). In vivo 3D endomicroscopy is
demonstrated in the rabbit colon, where individual colonic crypts are clearly visualized and measured. With
further improvements in DAQ technology, the imaging speed will be scalable to the hundreds of thousands of
axial lines/s supported by FDML lasers.
Ophthalmic OCT was performed using a novel, compact external cavity semiconductor laser at ~850
nm. Retinal imaging was demonstrated with a resolution of <7 microns in tissue at a speed of
16,000 axial scans per second. The coherence length of the laser is >10 mm, enabling an axial
measurement range of ~2.5 mm. Real-time display and data streaming capabilities enable video-rate
imaging of the retina at >30 frames per second. High-definition and three-dimensional imaging
were demonstrated on normal retinas. The resolution of <7 microns in the retina is, to our
knowledge, the highest resolution achieved in the retina with swept source OCT to date. The long
coherence length of the laser enables high-sensitivity measurements over a large axial measurement
range. The speed of 16,000 axial scans per second is comparable to current spectrometer-based
spectral/Fourier domain OCT systems. The low cost and small footprint of our laser (~10 cm x 20
cm) may enable the development of OCT for novel applications. Further improvements in speed
will be possible by using alternative scanning methods.
Retinal imaging ranks amongst the most important clinical applications for optical coherence
tomography (OCT) [1, 2]. The recent demonstration of increased sensitivity [3-6] in Fourier
Domain detection [7, 8] has opened the way for dramatically higher imaging speeds, up to axial
scan rates of several tens of kilohertz. However, these imaging speeds are still not sufficient for
high density 3D datasets and a further increase to several hundreds of kilohertz is necessary. In
this paper we demonstrate a swept laser source at 1050 nm with a sweep rate of 202 kHz. The
laser source provides ~10 mW average output power, up to 60 nm total sweep range and a
sensitivity roll off of less than 10 dB over 4 mm. In vivo 2D and 3D imaging of the human retina
at a record axial scan rate of 101 kHz is demonstrated. These results suggest that swept source
OCT has the potential to significantly outperform spectral/Fourier domain OCT for ophthalmic
imaging applications in the future.
Phase sensitive optical coherence tomography (OCT) can be used to obtain sub-nanometer
displacement measurements of biological and non-biological samples. This technique has many
applications, including detection of small amplitude surface motion, and high axial resolution OCT
phase microscopy. Doppler OCT is another type of phase sensitive imaging, where differential
phase measurements are used to detect fluid flow in biological specimens. For all types of phase
sensitive OCT, a light source with low phase noise is required in order to provide good
displacement sensitivity. High speed imaging is also necessary in order to minimize motion artifacts
and enable the detection of fast transient events. In this manuscript, buffered Fourier Domain Mode
Locked (FDML) lasers are demonstrated for ultrahigh-speed phase sensitive OCT detection. The
lasers are operated at sweep speeds of 42, 117, and 370 kHz, and displacement sensitivities of 39,
52, and 102 pm are achieved, respectively. These displacement sensitivities are comparable to
spectrometer-based phase sensitive OCT systems, but acquisition speeds 1.4 - 13x faster are
possible using buffered FDML lasers. An additional factor of √2 improvement in noise performance
is observed for differential phase measurements, which has important implications for Doppler
OCT. Dynamic measurements of rapid, small-amplitude piezoelectric transducer motion are
demonstrated. In general, buffered FDML lasers provide excellent displacement sensitivities at
extremely high sweep speeds for phase sensitive OCT measurements.
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