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 μm axial resolution in scattering tissue and approximately 3.2 μm 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.
©2004 Optical Society of America
Optical coherence tomography (OCT) is an emerging biomedical imaging technology that provides two-dimensional, cross-sectional, micron-scale images of biological tissues in vivo . Standard resolution OCT with 10–15 μm axial resolution has been applied extensively for imaging tissue microstructure in several medical specialties, ranging from ophthalmology to gastroenterology. Recently, ultrahigh resolution optical coherence tomography (UHR-OCT) with axial resolution of 1–3 μm was demonstrated using either femtosecond solid-state lasers or femtosecond lasers in combination with nonlinear optical fibers [2–5]. UHR-OCT imaging with 3 μm axial resolution has also been demonstrated in ophthalmology, enabling an improved visualization of intraretinal architecture compared to standard resolution OCT [6, 7]. However, femtosecond lasers are expensive and can be difficult to operate, thus presenting a major challenge to the widespread adoption of UHR-OCT imaging technology in the clinical setting. Superluminescent diode (SLD) sources are compact, robust, easy to operate, and much less expensive than femtosecond solid-state lasers. Until recently the bandwidths of commercial SLD sources were relatively limited. Consequently, OCT axial resolutions were limited to ~10 μm when SLD sources were used. The development of a broadband SLD light source for ultrahigh resolution OCT will greatly enhance the clinical utility of UHR-OCT imaging.
Broadband superluminescent sources for OCT imaging have been previously investigated, but to date in vivo ultrahigh resolution OCT imaging has not been possible. Broadband superluminescence generated from a titanium:sapphire crystal pumped with high-power lasers can provide ~2 μm OCT axial resolution [8, 9]. However, the power that can be coupled into a signal mode fiber (in the μW range) is too low for high-speed in vivo imaging [8, 9]. Ti:sapphire waveguides can be used to improve the coupling efficiency of the superluminescence into a single-mode fiber, but the power is still not sufficient for in vivo imaging [10–12]. Superluminescent diodes (SLD) are semiconductor high-gain optical amplifiers which generate amplified spontaneous emission. Early superluminescent diodes had a similar structure to diode lasers, except that antireflection coatings were applied to the diode facets to reduce feedback and inhibit lasing. However, spectral modulation of the diode output and lasing from parasitic feedback limited the output power of these designs to a few milliwatts. The use of angled waveguide structures further reduced feedback to enable higher power operation without spectral modulation or lasing [13–15]. The use of quantum well structures enabled broad gain bandwidths to be achieved at lower current densities than was possible with “bulk” heterostructure devices .
In order to further increase the optical output bandwidth while maintaining high output power, wavelength division multiplexing (WDM) of spectrally shifted SLDs can be performed. Early work demonstrated improvement in axial resolution from 10 μm to 6 μm using two wavelength division multiplexed SLDs . In another study, using a dual-beam OCT approach, two spectrally displaced SLD beams were combined to achieve an effective bandwidth of 50 nm, corresponding to an OCT axial resolution of 6–7 μm . However the output powers of these sources were low and thus limited signal-to-noise performance for in vivo OCT imaging applications. Furthermore, the total optical bandwidth was not sufficient to achieve ultrahigh axial resolutions of 2–3 μm, which is possible with femtosecond solid-state laser light sources. In this paper, we demonstrate in vivo ultrahigh resolution OCT imaging using a new broadband superluminescent diode light source. The broadband source consists of two independent SLD diodes where the two optical outputs are multiplexed to achieve a total bandwidth of 155 nm and > 4 mW total CW output power. An axial resolution of ~2.3 μm was obtained in scattering tissue and an axial resolution of ~3.2 μm was obtained in the retina. The image quality and resolution in both scattering tissue and the retina are comparable to those obtained using femtosecond solid-state laser sources. This result demonstrates the ability to achieve in vivo ultrahigh resolution OCT imaging without the need for femtosecond solid-state lasers.
The broadband SLD source was a new prototype developed by Superlum Diodes, Ltd. and consists of two spectrally multiplexed, independently driven SLD diodes operating at 840 nm and 920 nm, respectively. An SLD diode based on a SQW (GaAl)As heterostructure  and a second recently-developed SLD diode based on a SQW (InGa)As/(AlGa)As heterostructure with graded-index waveguides  were used. The SLDs have optical outputs with overlapping spectral bands that can be combined with a broadband fiber coupler. A custom built broadband single-mode fiber Y-coupler based on fiber GRIN microlenses and miniature partially transmitting mirrors with dielectric multilayer coatings was developed to spectrally multiplex the SLD outputs. In the spectral range of 750–1100 nm, a coupling ratio of close to 50% and an insertion loss of less than 1 dB were achieved with this coupler. The combined SLD output provides 155 nm of bandwidth at a center wavelength of 890 nm with > 4 mW of CW output power. Compared to a solid-state laser, this broadband SLD source is quite compact and has a total footprint of only 31 × 26 × 15 cm including the power supply, or 31 × 15 × 5 cm for the SLD and multiplexer package alone. The total cost of this light source is about an order of magnitude less than that of a typical commercial Ti:sapphire femtosecond laser.
Typical OCT systems, including the systems used for these experiments, usually operate at a detection frequency somewhere between 100 kHz and 10 MHz. Since the SLD source has low excess RF intensity noise in this range, dual-balanced detection is not required and high sensitivity can be obtained by using a single detector. However, the SLD source is sensitive to optical feedback, so special care was exercised to suppress all back reflections in the system to less than -30 dB. The reteroreflected reference arm power is within this limit and the typical retroreflected sample arm power is even lower. A custom fabricated broadband 50/50 fiber optic coupler (Gould Electronics Inc.) that supported the full spectrum of the SLD source was used for the Michelson interferometer. The reference arm of the interferometer contains adjustable wedges of BK7 glass and fused silica (FS) for dispersion compensation. When conducting ophthalmic imaging, the reference arm also contains a 24-mm (normal eye length) water cell to match the dispersion from the vitreous of the eye. The sample arm consists of either an OCT microscope (for in vivo imaging of the hamster cheek pouch) or a modified ophthalmic slit lamp (for in vivo retinal imaging). Polarization controllers were used in the reference and sample arms to match the polarization states of the interfering fields, maximizing the output of the interferometer. Figure 1 illustrates the schematic of the OCT system used in this experiment.
Figure 2(a) shows the individual output spectra of the two superluminescent diodes. Figure 2(b) shows the fiber-coupled spectrum of the broadband SLD source, demonstrating a full-width-half-maximum bandwidth of 155 nm. Up to 1.6 mW of SLD power was available at the sample arm. The interferometric point spread function was measured using an attenuated isolated reflection from a mirror. The coherence point spread function of the broadband SLD source was measured by placing a mirror after the imaging microscope in the sample arm. The interferometric point spread function from a mirror with an OD 3.0 filter was measured [Fig. 2(c)] and shows a 3.0 μm OCT axial resolution in air, corresponding to approximately 2.3 μm in tissue. Because the spectrum of the light source has sharp edges and spectral modulation, sidelobes are present in the point spread function. However, since the intensity point spread function is the square of the field point spread function, these sidelobes do not produce significant image artifacts except when isolated high reflecting features are present. Figure 2(d) shows the point spread function after logarithmic demodulation, demonstrating a sensitivity of 102 dB. For these measurements, axial scanning was performed at a velocity of 82 mm/sec with a Doppler frequency of 205 kHz and detection bandwidth of 54 kHz.
To demonstrate in vivo ultrahigh resolution OCT imaging in scattering tissue, an everted hamster cheek pouch was imaged using a microscope for beam delivery. Following general anesthesia with diazepam and pentobarbital sodium, the cheek pouch was everted and the animal was secured to an imaging stage. The broadband SLD had ~4 mW total CW power output, of which 1.6 mW was incident on the hamster cheek pouch. The image taken from the in vivo sample had a total scan depth of 1.5 mm in tissue and a transverse scan length of 2 mm. Transverse resolution was 5 μm and axial resolution was ~2.3 μm in tissue. The total imaging time to acquire 1000 axial scans was about 40 seconds. For these imaging measurements, axial scanning was performed at a velocity of 82 mm/sec with a Doppler frequency of 205 kHz and detection bandwidth of 54 kHz.
For in vivo ultrahigh resolution OCT ophthalmic imaging, a modified slitlamp capable of generating arbitrary scan patterns on the retina was used. The modified slitlamp is similar to those previous reported for ultrahigh resolution ophthalmic OCT imaging of the retina . The water in the vitreous absorbs strongly at wavelengths above 920 nm and limits the bandwidth that can be used for retinal imaging . A 24-mm-length water cell was used in the reference arm in order to balance the dispersion in the eye. Absorption measurements performed on this water cell also confirmed that wavelengths longer than 920 nm were absorbed. The light incident on the eye was filtered to remove long wavelengths that would be absorbed, resulting in a bandwidth of 120 nm for ophthalmic imaging. The interferometric axial point spread function was measured using an isolated attenuated reflection from a mirror and was 4.3 μm in air, corresponding to 3.2 μm in tissue. Using 750 μW of incident power at the slitlamp output, well below the ANSI safety limit for retinal exposure, a sensitivity of 94 dB was obtained. For ophthalmic imaging, axial scanning was performed at a velocity 410 mm/sec with a Doppler frequency of 1 MHz and detection bandwidth of 170 kHz. The axial scan length was 1.5 mm in tissue and the scan repetition rate was approximately 140 scans per second. Each ophthalmic image consists of 600 A-scans with an imaging scan time of approximately 4 seconds. This acquisition time was identical to that using a femtosecond solid-state laser light source and sufficiently short for the subject to keep the eye open and maintain fixation.
Figure 3 shows an example of in vivo ultrahigh resolution OCT imaging in the hamster cheek pouch using the broadband SLD light source. This image has an axial resolution of approximately 2.3 μm in tissue and a transverse resolution of approximately 5 μm. A glass coverslip was used on the surface of the exposed cheek pouch epithelium in order to reduce the high specular reflection caused by the large index mismatch from air to tissue. A cross-correlation algorithm was used to remove the motion artifacts caused by the breathing of the animal. No additional image processing techniques were applied to the image. This OCT image taken with the broadband SLD light source has image resolution and quality comparable to ultrahigh resolution OCT images of the hamster cheek pouch taken with a solid-state laser light source . The stratum cornium is seen as a highly backscattering layer at the top of the cheek pouch, followed by the low backscattering epithelium layer. The muscularis layers and connective tissues below the epithelium layer can also be readily seen in this image. Blood vessels are clearly visible, which causes characteristic shadowing of the OCT signal below the level of the vessels.
Figure 4 shows an example of in vivo ultrahigh resolution OCT imaging in the human retina using the broadband SLD light source. This image is 6 mm long in the transverse direction, centered on the fovea of the retina. The OCT axial resolution was approximately 3.2 μm in the retina and transverse resolution was 15–20 μm. A cross-correlation algorithm was used to remove the motion artifacts caused by axial motion of the subject. A false-color mapping similar to that used in the commercial ophthalmic OCT system (StratusOCT, Carl Zeiss Meditec, Dublin, CA) was used in order to better highlight individual intraretinal layers . No additional image processing techniques were applied to the image. This ultrahigh resolution ophthalmic OCT image taken with the broadband SLD has image resolution and quality similar to ultrahigh resolution ophthalmic OCT images previously reported [6, 7].
When comparing the ultrahigh resolution OCT image (Fig. 4) to a standard 10 μm resolution OCT image taken with the commercial StratusOCT system from the same normal subject (Fig. 5), the intraretinal layers are much better delineated and visualized in the ultrahigh resolution OCT image. The first highly backscattering layer of the nerve fiber layer is visualized as a red and yellow layer at the top of the retina. The low backscattering layers of the ganglion cell layer (GCL), the inner nuclear layer (INL), and the outer nuclear layer (ONL) are visualized as blue-black layers. The scattering layers of the inner plexiform layer (IPL) and outer plexiform layer (OPL) are visualized as green-yellow layers in between the nuclear layers. In the outer retina, the thin external limiting membrane (ELM) is seen as a thin green layer below the outer nuclear layer. The first highly backscattering layer of the outer retina is the junction between the inner and outer segments (IS/OS), and the second highly backscattering layer is the retinal pigment epithelium (RPE). In the standard 10 μm resolution OCT image (Fig. 5), the thin intraretinal layers, such as the ganglion cell layer and the external limiting membrane, can not be visualized clearly. Figure 6 shows 2x enlargements of the foveal region from the ultrahigh resolution OCT (Fig. 4) and standard resolution OCT image (Fig. 5). Figure 6 demonstrates that ultrahigh resolution OCT performed with a broadband SLD source has the ability to improve visualization and delineation of small intraretinal features over standard resolution OCT. Retinal features such as the external limiting membrane, the ganglion cell layer, and the integrity of the photoreceptor segments are much better visualized in the ultrahigh resolution OCT image.
We have demonstrated in vivo ultrahigh resolution imaging using a superluminescent diode (SLD) light source. A broadband optical output was achieved by multiplexing the outputs from two SLDs operating at 840 nm and 920 nm. This light source generated 155 nm bandwidth with 4 mW output power. Ultrahigh resolution OCT imaging with 2.3 μm axial resolution in scattering tissue and 3.2 μm resolution in the retina has been demonstrated. The image resolution for retinal imaging was limited by water absorption in the eye. The development of SLD devices at shorter wavelengths, which do not overlap the onset of water absorption at 920 nm, should improve resolution for retinal imaging in the future . Although output powers are limited, the broadband SLD light source produces ultrahigh resolution OCT images which are comparable to those obtained using femtosecond solid state lasers [2–7]. These results demonstrate the ability to achieve in vivo ultrahigh resolution OCT imaging using a compact, easy to operate, and relatively inexpensive SLD light source. The development of these new light sources should greatly enhance the availability of ultrahigh resolution OCT technology, especially in clinical applications such as ophthalmology.
Supported in part by NIH contracts R01-EY11289-16, R01-EY13178, and P30-EY13078, NSF contract ECS-0119452, Air Force Office of Scientific Research contract F49620-98-1-0139, Medical Free Electron Laser Program contracts F49620-01-1-0186, and by Carl Zeiss Meditec. James G. Fujimoto receives royalties from intellectual property licensed by M.I.T. to Carl Zeiss Meditec.
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