Ultrahigh speed spectral-domain optical coherence ... - OSA Publishing

Ultrahigh speed spectral-domain optical coherence microscopy Hsiang-Chieh Lee,1 Jonathan J. Liu,1 Yuri Sheikine,2,4 Aaron D. Aguirre,1,3 James L. Connolly,2 and James G. Fujimoto1,* 1

Department of Electrical Engineering and Computer Science, and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA 2 Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA 3 Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA 4 Alternative spelling of this author's name is Yury Sheykin * [email protected]

Abstract: We demonstrate a compact, ultrahigh speed spectral-domain optical coherence microscopy (SD-OCM) system for multiscale imaging of specimens at 840 nm. Using a high speed 512-pixel line scan camera, an imaging speed of 210,000 A-scans per second was demonstrated. Interchangeable water immersion objectives with magnifications of 10×, 20×, and 40× provided co-registered en face cellular-resolution imaging over several size scales. Volumetric OCM data sets and en face OCM images were demonstrated on both normal and pathological human colon and kidney specimens ex vivo with an axial resolution of ~4.2 µm, and transverse resolutions of ~2.9 µm (10×), ~1.7 µm (20×), and ~1.1 µm (40×) in tissue. In addition, en face OCM images acquired with high numerical aperture over an extended field-of-view (FOV) were demonstrated using image mosaicking. Comparison between en face OCM images among different transverse and axial resolutions was demonstrated, which promises to help the design and evaluation of imaging performance of Fourier domain OCM systems at different resolution regimes. ©2013 Optical Society of America OCIS codes: (170.4500) Optical coherence tomography; (170.3880) Medical and biological imaging; (170.6900) Three-dimensional microscopy; (180.1790) Confocal microscopy.

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Received 16 Apr 2013; revised 12 Jun 2013; accepted 12 Jun 2013; published 1 Jul 2013

1 August 2013 | Vol. 4, No. 8 | DOI:10.1364/BOE.4.001236 | BIOMEDICAL OPTICS EXPRESS 1236

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1. Introduction Optical coherence tomography (OCT) enables real time, three-dimensional, high-resolution imaging of intact tissue and specimens [1]. While OCT can achieve extremely high axial resolution [2], the transverse resolution is not sufficient to reveal cellular or subcellular features. Optical coherence microscopy (OCM) combines low coherence detection with conventional confocal microscopy to improve the transverse resolution of OCT images [3,4]. In confocal microscopy, a high numerical aperture (NA) optical design is essential to provide fine axial sectioning capability and reject unwanted light from out-of-focus regions. Confocal microscopy is therefore vulnerable to aberration and multiple scattering in biological specimens, which typically limits the imaging depth. In comparison, OCM significantly enhances the maximum imaging depth in scattering materials by improving rejection of scattered light using coherence gating, which also relaxes the constraint of extremely high NA optics required to obtain axial sectioning in confocal microscopy [3,4]. However, there still a trade off between the depth-of-focus (DOF) and transverse resolution in OCM images. Recent studies have used beam shaping or computational methods to demonstrate increased DOF in OCT or OCM imaging without sacrificing lateral resolution [5–13]. Although an extended DOF can be achieved using a Bessel-beam illumination and collection with an axicon lens [5– 8] or binary phase filter [9], sensitivity losses of up to tens of decibels were reported. An extended focus OCT image was demonstrated based on digital focusing by solving the inverse scattering problem without the need for beam shaping [10–13]. However, digital focusing is computational expensive and requires phase stable acquisition along consecutive axial scans. OCM was originally developed using time domain detection, which allows en face imaging of scattering media [3]. Recently, an integrated OCT and OCM system was demonstrated, providing images with an axial resolution of