© 2007 Nature Publishing Group

Three-dimensional endomicroscopy
using optical coherence tomography
DESMOND C. ADLER1, YU CHEN1, ROBERT HUBER1,2, JOSEPH SCHMITT3, JAMES CONNOLLY4
AND JAMES G. FUJIMOTO1*
1Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge,
Massachusetts 02139, USA
2Lehrstuhl fu¨r BioMolekulare Optik, Fakulta¨t fu¨r Physik, Ludwig-Maximilians-Universita¨t Mu¨nchen, 80538 Mu¨nchen, Germany
3Lightlab Imaging, Westford, Massachusetts 01886, USA
4Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
*e-mail: jgfuji@mit.edu
Published online: 25 November 2007; doi:10.1038/nphoton.2007.228
Optical coherence tomography enables micrometre-scale, subsurface imaging of biological tissue by measuring the magnitude and
echo time delay of backscattered light. Endoscopic optical coherence tomography imaging inside the body can be performed using
fibre-optic probes. To perform three-dimensional optical coherence tomography endomicroscopy with ultrahigh volumetric
resolution, however, requires extremely high imaging speeds. Here we report advances in optical coherence tomography
technology using a Fourier-domain mode-locked frequency-swept laser as the light source. The laser, with a 160-nm tuning range
at a wavelength of 1,315 nm, can produce images with axial resolutions of 5–7 mm. In vivo three-dimensional optical coherence
tomography endomicroscopy is demonstrated at speeds of 100,000 axial lines per second and 50 frames per second. This enables
virtual manipulation of tissue geometry, speckle reduction, synthesis of en face views similar to endoscopic images, generation of
cross-sectional images with arbitrary orientation, and quantitative measurements of morphology. This technology can be scaled
to even higher speeds and will open up three-dimensional optical-coherence-tomography endomicroscopy to a wide range of
medical applications.
Optical coherence tomography (OCT) performs micrometre-scale,
cross-sectional imaging by measuring the echo time delay of
backscattered light1. It is a fibre-optic technique, enabling
internal body imaging with fibre-optic probes2. Two-dimensional
endoscopic OCT has been demonstrated with axial resolutions of
2.4–3.7 mm using femtosecond lasers3,4. Three-dimensional
endoscopic OCT (3D-OCT) promises to provide more complete
characterization of tissue structure, but requires extremely high
imaging speeds and data processing rates.
Time-domain OCT (ref. 5) uses low-coherence reflectometry,
with imaging speeds of 4,000–8,000 axial lines per second
(4–8 kHz) achieved using reference-arm grating phase delay
lines6–10. Optical frequency-domain reflectometry (OFDR) using
frequency-swept lasers is well established for measuring
reflections in photonic devices11–15. The use of swept lasers for
OCT was demonstrated a decade ago16–18; however, it was only
recently recognized that Fourier-domain detection using swept
lasers or spectrometers dramatically improves sensitivity and
imaging speed19–21.
Frequency-swept lasers are a key technology for high-speed
‘swept source’ OCT imaging. The sweep repetition rate, tuning
range, and instantaneous linewidth of the laser determine the
imaging speed, axial resolution and ranging depth of the OCT
system, respectively. Swept lasers using a tunable filter composed
of a diffraction grating and a rotating polygon mirror have
achieved sweep rates of 15.7–115 kHz over tuning ranges of
74–80 nm (refs 22,23). Using a similar laser with a tuning range
of 111–125 nm, endoscopic 3D-OCT imaging has been
demonstrated in the porcine oesophagus and coronary artery at
sweep rates of 10 kHz and 54 kHz, respectively24,25.
Conventional swept lasers suffer fundamental performance
limitations as sweep rate is increased, because lasing must
repeatedly build up from spontaneous emission during the
sweep. This degrades the power, tuning range, and instantaneous
linewidth26. Recently, Fourier-domain mode-locked (FDML)
lasers were demonstrated to achieve high performance at high
sweep rates27–29. Fourier-domain mode-locked lasers use a long
fibre cavity with a semiconductor amplifier and fibre
Fabry–Pe´rot tunable filter (FFP-TF). The filter is tuned
synchronously to the cavity round trip time in a quasi-stationary
operating regime, giving sweep rates up to 370 kHz over tuning
ranges of 100 nm (ref. 28).
This paper describes 3D-OCTendomicroscopy using an FDML
laser operating at a sweep rate of 100 kHz with a 160-nm tuning
range. Axial resolutions of 5–7 mm are achieved, representing the
highest endoscopic speed and resolution obtained so far with a
swept-source OCT imaging system. The system uses optical
clocking to provide real-time image capture at 50 frames per
second with 2,000 axial lines per frame. In vivo imaging is
demonstrated in the rabbit colon using a spiral-scanning fibre
endoscope probe. Over an 8.8-mm length of colon, 1.1 gigavoxels
with a 3D resolution of 9mm  20 mm  7 mm (1,260 mm3) are
acquired in 17.7 s. Epithelial structures linked to neoplastic
changes are detected. A variety of visualization techniques are
ARTICLES
nature photonics | VOL 1 |DECEMBER 2007 | www.nature.com/naturephotonics 709