High speed optical coherence microscopy with autofocus adjustment and a miniaturized endoscopic imaging probe

Optical coherence microscopy (OCM) is a promising technique for high resolution cellular imaging in human tissues. An OCM system for high-speed en face cellular resolution imaging was developed at 1060 nm wavelength at frame rates up to 5 Hz with resolutions of < 4 µm axial and < 2 µm transverse. The system utilized a novel polarization compensation method to combat wavelength dependent source polarization and achieve broadband electro-optic phase modulation compatible with ultrahigh axial resolution. In addition, the system incorporated an auto-focusing feature that enables precise, near real-time alignment of the confocal and coherence gates in tissue, allowing user-friendly optimization of image quality during the imaging procedure. Ex vivo cellular images of human esophagus, colon, and cervix as well as in vivo results from human skin are presented. Finally, the system design is demonstrated with a miniaturized piezoelectric fiber-scanning probe which can be adapted for laparoscopic and endoscopic imaging applications.

[1]  Wibool Piyawattanametha,et al.  Two-axis MEMS Scanning Catheter for Ultrahigh Resolution Three-dimensional and En Face Imaging. , 2007, Optics express.

[2]  J. Fujimoto,et al.  Swept source optical coherence microscopy using a Fourier domain mode-locked laser. , 2007, Optics express.

[3]  G. Fedder,et al.  A two-axis electrothermal micromirror for endoscopic optical coherence tomography , 2004, IEEE Journal of Selected Topics in Quantum Electronics.

[4]  Zhaoming Zhu,et al.  Polarization properties of supercontinuum spectra generated in birefringent photonic crystal fibers , 2004 .

[5]  Wolfgang Rudolph,et al.  Comparative study of confocal and heterodyne microscopy for imaging through scattering media , 1996 .

[6]  B E Bouma,et al.  Forward-imaging instruments for optical coherence tomography. , 1997, Optics letters.

[7]  I Hartl,et al.  Ultrahigh resolution real time OCT imaging using a compact femtosecond Nd:Glass laser and nonlinear fiber. , 2003, Optics express.

[8]  D. Tank,et al.  A Miniature Head-Mounted Two-Photon Microscope High-Resolution Brain Imaging in Freely Moving Animals , 2001, Neuron.

[9]  Jun Zhang,et al.  Three-dimensional endoscopic optical coherence tomography by use of a two-axis microelectromechanical scanning mirror , 2006 .

[10]  Brett E Bouma,et al.  Two-axis magnetically-driven MEMS scanning catheter for endoscopic high-speed optical coherence tomography. , 2007, Optics express.

[11]  C. Boccara,et al.  Ultrahigh-resolution full-field optical coherence tomography. , 2004, Applied optics.

[12]  J. Nelson,et al.  Stable carrier generation and phase-resolved digital data processing in optical coherence tomography. , 2001, Applied optics.

[13]  A W Smeulders,et al.  Robust autofocusing in microscopy. , 2000, Cytometry.

[14]  Xingde Li,et al.  Dispersion management up to the third order for real-time optical coherence tomography involving a phase or frequency modulator. , 2004, Optics express.

[15]  J. Fujimoto,et al.  Buffered Fourier domain mode locking: Unidirectional swept laser sources for optical coherence tomography imaging at 370,000 lines/s. , 2006, Optics letters.

[16]  Thomas D. Wang,et al.  Miniature near-infrared dual-axes confocal microscope utilizing a two-dimensional microelectromechanical systems scanner. , 2007, Optics letters.

[17]  J G Fujimoto,et al.  High-resolution optical coherence microscopy for high-speed, in vivo cellular imaging. , 2003, Optics letters.

[18]  W. Denk,et al.  Miniature random-access fiber scanner for in vivo multiphoton imaging , 2007 .

[19]  R. Webb,et al.  In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast. , 1995, The Journal of investigative dermatology.

[20]  Timothy J Muldoon,et al.  High-resolution imaging in Barrett's esophagus: a novel, low-cost endoscopic microscope. , 2008, Gastrointestinal endoscopy.

[21]  A. Polglase,et al.  Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. , 2004, Gastroenterology.

[22]  Yingtian Pan,et al.  High-speed optical coherence tomography using fiberoptic acousto-optic phase modulation. , 2003, Optics express.

[23]  I. Alex Vitkin,et al.  Dynamic focus control in high-speed optical coherence tomography based on a microelectromechanical mirror , 2004 .

[24]  N Iftimia,et al.  Rapid wavelength-swept spectrally encoded confocal microscopy. , 2005, Optics express.

[25]  J. Izatt,et al.  Optical Coherence Tomography and Microscopy in Gastrointestinal Tissues , 1996, Advances in Optical Imaging and Photon Migration.

[26]  G. Ripandelli,et al.  Optical coherence tomography. , 1998, Seminars in ophthalmology.

[27]  Zhongping Chen,et al.  Fiber-optic-bundle-based optical coherence tomography. , 2005, Optics letters.

[28]  Siavash Yazdanfar,et al.  Real-time, high velocity-resolution color Doppler optical coherence tomography. , 2002, Optics letters.

[29]  R Richards-Kortum,et al.  Detection and diagnosis of oral neoplasia with an optical coherence microscope. , 2004, Journal of biomedical optics.

[30]  A. Polglase,et al.  A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract. , 2005, Gastrointestinal endoscopy.

[31]  Zhongping Chen,et al.  Phase-resolved optical coherence tomography and optical Doppler tomography for imaging blood flow in human skin with fast scanning speed and high velocity sensitivity. , 2000, Optics letters.

[32]  J. Fujimoto,et al.  Optical coherence microscopy in scattering media. , 1994, Optics letters.

[33]  G. Fedder,et al.  Endoscopic optical coherence tomography based on a microelectromechanical mirror. , 2001, Optics letters.

[34]  Improved phase modulation for an en-face scanning three-dimensional optical coherence microscope , 2004 .

[35]  Christopher H Contag,et al.  Functional imaging of colonic mucosa with a fibered confocal microscope for real-time in vivo pathology. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[36]  C. Menyuk,et al.  Nonlinear polarization evolution of ultrashort pulses in microstructure fiber. , 2004, Optics letters.

[37]  David D Sampson,et al.  Delay and dispersion characteristics of a frequency-domain optical delay line for scanning interferometry. , 2003, Journal of the Optical Society of America. A, Optics, image science, and vision.

[38]  Joseph M. Schmitt,et al.  An optical coherence microscope with enhanced resolving power , 1997 .

[39]  J. Fujimoto,et al.  High-resolution line-scanning optical coherence microscopy. , 2007, Optics letters.

[40]  Qienyuan Zhou,et al.  Three-dimensional imaging of the human retina by high-speed optical coherence tomography. , 2003, Optics express.

[41]  G. Kino,et al.  Silicon-micromachined scanning confocal optical microscope , 1998 .

[42]  Olav Solgaard,et al.  Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two- dimensional scanning mirror. , 2006, Optics letters.

[43]  A. Fercher,et al.  Dynamic coherent focus OCT with depth-independent transversal resolution , 1999 .

[44]  Yingtian Pan,et al.  Dispersion compensation in high-speed optical coherence tomography by acousto-optic modulation. , 2005, Applied optics.

[45]  Claudio Vinegoni,et al.  Spectroscopic spectral-domain optical coherence microscopy. , 2006, Optics letters.

[46]  J. Fujimoto,et al.  High-speed phase- and group-delay scanning with a grating-based phase control delay line. , 1997, Optics letters.

[47]  Xingde Li,et al.  Fiber-optic scanning two-photon fluorescence endoscope. , 2006, Optics letters.

[48]  S Yazdanfar,et al.  Electrostatic micromachine scanning mirror for optical coherence tomography. , 2003, Optics letters.

[49]  Angelique Kano,et al.  Design and demonstration of a miniature catheter for a confocal microendoscope. , 2004, Applied optics.

[50]  G. Berden,et al.  Detectors: Time-Domain TerahertzScience Improves RelativisticElectron-Beam Diagnostics , 2002 .

[51]  Hiroshi Miyajima,et al.  A MEMS electromagnetic optical scanner for a commercial confocal laser scanning microscope , 2003 .

[52]  Hyun Joon Shin,et al.  Single fiber confocal microscope with a two-axis gimbaled MEMS scanner for cellular imaging. , 2006, Optics express.