We consider the use of single-photon counting detectors in coherence-domain imaging. Detectors operated in this mode exhibit reduced noise, which leads to increased sensitivity for weak light sources and weakly reflecting samples. In particular, we experimentally demonstrate the possibility of using superconducting single-photon detectors (SSPDs) for optical coherence-domain reflectometry (OCDR). These detectors are sensitive over the full spectral range that is useful for carrying out such imaging in biological samples. With counting rates as high as 100 MHz, SSPDs also offer a high rate of data acquisition if the light flux is sufficient.

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Here we present new technology for optical coherence tomography (OCT) that enables ultrahigh-resolution, non-invasive in vivo ophthalmologic imaging of retinal and corneal morphology with an axial resolution of 2-3μm. This resolution represents a significant advance in performance over the 10-15μm resolution currently available in ophthalmic OCT systems and, to our knowledge, is the highest resolution for in vivo ophthalmologic imaging achieved to date. This resolution enables in vivo visualization of intraretinal and intra-corneal architectural morphology that had previously only been possible with histopathology. We demonstrate image processing and segmentation techniques for automatic identification and quantification of retinal morphology. Ultrahigh-resolution OCT promises to enhance early diagnosis and objective measurement for tracking progression of ocular diseases, as well as monitoring the efficacy of therapy. Current clinical practice emphasizes the development of techniques to diagnose disease in its early stages, when treatment is most effective and irreversible damage can be prevented or delayed. In ophthalmology, the precise visualization of pathology is especially critical for the diagnosis and staging of ocular diseases. Therefore, new imaging techniques have been developed to augment conventional fundoscopy and slit-lamp biomicroscopy. Ultrasonography is routinely used in ophthalmology, but requires physical contact with the eye and has axial resolutions of approximately 200μm (ref. 1). High-frequency ultrasound enables approximately 20μm axial resolutions, but due to limited penetration, only anterior eye structures can be imaged2. Confocal microscopy has been used to image the cornea with sub-micrometer transverse resolution3. Scanning laser ophthalmoscopy enables en face fundus imaging with micron-scale transverse and approximately 300μm axial resolution4,5. None of these techniques, however, permits high-resolution, cross-sectional imaging of the retina in vivo. Recently, optical coherence tomography (OCT) has emerged as a promising new technique for high-resolution, cross-sectional imaging6,7. OCT is attractive for ophthalmic imaging because image resolutions are 1-2 orders of magnitude higher than conventional ultrasound, imaging can be performed non-invasively and in real time, and quantitative morphometric information can be obtained. OCT is somewhat analogous to ultrasound imaging except that it uses light instead of sound. High-resolution, cross-sectional images are obtained by measuring the echo time delay of reflected infrared light using a technique known as low coherence interferometry8,9. OCT imaging was first demonstrated in the human retina in vitro6 and in vivo10,11. Recently, it has been extended to a wide range of other non-transparent tissues to function as a type of optical biopsy12-15. To date, however, the most important clinical applications of OCT have been retinal imaging in ophthalmic diagnosis7,16-22. Current ophthalmic OCT systems have 10-15μm axial resolution and pr...

Ultrahigh-resolution optical coherence tomography (OCT) by use of state of the art broad-bandwidth femtosecond laser technology is demonstrated and applied to in vivo subcellular imaging. Imaging is performed with a Kerr-lens mode-locked Ti:sapphire laser with double-chirped mirrors that emits sub-two-cycle pulses with bandwidths of up to 350 nm, centered at 800 nm. Longitudinal resolutions of ~1mum and transverse resolution of 3mum, with a 110-dB dynamic range, are achieved in biological tissue. To overcome depth-of-field limitations we perform zone focusing and image fusion to construct a tomogram with high transverse resolution throughout the image depth. To our knowledge this is the highest longitudinal resolution demonstrated to date for in vivo OCT imaging.

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