The objective of this study was to develop and verify anew technique for monitoring the progression of osteoarthritis (OA) by combining a rat model with the imaging modality optical coherence tomography (OCT). Time-sequential, in vivo, OCT imaging was performed on the left femoral condyles of 12 Wistar rats following sodium-iodoacetic acid-induced OA progression. The right femoral condyles (untreated) were also imaged and served as controls. Imaging was performed on days 0, 10, 20, 30, and 60 with an OCT system capable of acquiring images at four frames per second and an axial resolution of 5 pin. Progressive changes were analyzed using an OA scoring system. OCT successfully identified progressive cartilage degeneration as well as alteration of the cartilage/bone interface. Significant changes to both of these structures were observed in the sodium-iodoacetic acid-injected condyles. Structural changes detected with OCT were confirmed histologically. OCT in combination with a well-known model used in arthritis research represents a powerful tool for following degenerative joint disease progression in a given animal by detecting changes to the cartilage/bone interface and articular cartilage. (c) 2006 Orthopaedic Research Society.

We present a semi-analytical model of optical coherence tomography (OCT) taking into account multiple scattering. The model rests on the assumptions that the measured portion of the backscattercd sample field is spatially coherent and that the sample is motionless relative to measurement time. This allows modeling an OCT signal as a sum of spatially coherent fields with random phase arguments - constant during measurement time - caused by multiple scattering. We calculate the mean OCT signal from classical results of statistical optics and a Monte Carlo simulation. Our model is shown to be in very good agreement with a whole range of experimental data gathered in a comprehensive study of cross-talk in wide-field OCT realized with spatially coherent illumination. The study consists of depth scan measurements of a mirror covered with an aqueous suspension of microspheres. We investigate the dependence of cross-talk on important optical system parameters, as well as on some relevant sample properties. We discuss the more complex OCT models based on the extended Huygens-Fresnel principle, which rest on different assumptions since they assume partially coherent interfering fields.

We present a comprehensive study of multiple-scattering effects in wide-field optical coherence tomography (OCT) realized with spatially coherent illumination. Imaging a sample made of a cleaved mirror embedded in an aqueous suspension of microspheres revealed that, despite temporal coherence gating, multiple scattering can induce significant coherent optical cross talk. The latter is a serious limitation to the method, since it prevents shot-noise-limited detection and diffraction-limited imaging in scattering samples. We investigate the dependence of cross talk on important system design parameters, as well as on some relevant sample properties. The agreement between theoretical and experimental results for the wide range of parameters investigated was very good, in both the lateral and the axial dimensions. This further confirms the validity of the model developed in our companion paper [J. Opt. Soc. Am. A 22, 1369-1379 (2005)].

BACKGROUND:Ultrahigh-resolution optical coherence tomography (OCT) has an axial resolution of <5 microm, 2 to 3 times finer than standard OCT. This study investigates ultrahigh-resolution and three-dimensional OCT for ex vivo imaging of the large and small intestines and correlates images with histology. METHODS:Ultrahigh-resolution OCT imaging was performed on fresh surgical specimens from the large and small intestines in the pathology laboratory, and images were correlated with histology. OCT was performed at 1.3-microm wavelength with 4.5-microm axial x 11-microm transverse resolution and at 1.1-microm wavelength with 3.5-microm axial x 6-microm transverse resolution. Three-dimensional OCT also was investigated. RESULTS:Normal and pathologic areas from 23 surgical specimens of the large and small intestines were imaged. Ultrahigh-resolution OCT distinguished the epithelial layer of the mucosa and visualized individual villi, glands, and crypts. Finer transverse resolutions improved visualization of features, e.g., the epithelium, but reduced the depth of field. Architectural distortion of glands from inflammatory and neoplastic processes was observed. Three-dimensional rendering enabled visualization of surface pit pattern and mucosal folds as well as subsurface crypt microstructure. CONCLUSIONS:This study evaluates new OCT technology and can provide a baseline for interpreting future ultrahigh-resolution endoscopic OCT studies.

We present a new light source for parallel Optical Coherence Tomography (OCT) based on multiple waveguides written in Ti:sapphire. Each channel can generate a spectrum of 174 nm bandwidth centered at 772 nm, with an optical power on sample of 30 mu W. A system depth resolution of 1.9 mu m is obtained, which correspond to 1.5 mu m in tissue.

We present a new model of optical coherence tomography (OCT) taking into account multiple scattering. A theoretical analysis and experimental investigation reveals that in OCT, despite multiple scattering, the field backscattered from the sample is generally spatially coherent and that the resulting interference signal with the reference field is stationary relative to measurement time. On the basis of this result, we model an OCT signal as a sum of spatially coherent fields with random-phase arguments--constant during measurement time--caused by multiple scattering. We calculate the mean of such a random signal from classical results of statistical optics and a Monte Carlo simulation. OCT signals predicted by our model are in very good agreement with a depth scan measurement of a sample consisting of a mirror covered with an aqueous suspension of microspheres. We discuss other comprehensive OCT models based on the extended Huygens-Fresnel principle, which rest on the assumption of partially coherent interfering fields.

Current spectroscopic optical coherence tomography (OCT) methods rely on a posteriori numerical calculation. We present an experimental alternative for accessing spectroscopic information in OCT without post-processing based on wavelength de-multiplexing and parallel detection using a diffraction grating and a smart pixel detector array. Both a conventional A-scan with high axial resolution and the spectrally resolved measurement are acquired simultaneously. A proof-of-principle demonstration is given on a dynamically changing absorbing sample. The method's potential for fast spectroscopic OCT imaging is discussed. The spectral measurements obtained with this approach are insensitive to scan non-linearities or sample movements.

A new femtosecond pump-probe spectroscopy technique is demonstrated that permits the high-speed, parallel acquisition of pump-probe measurements at multiple wavelengths. This is made possible by use of a novel, two-dimensional smart pixel detector array that performs amplitude demodulation in real time on each pixel. This detector array can not only achieve sensitivities comparable with lock-in amplification but also simultaneously performs demodulation of probe transmission signals at multiple wavelengths, thus permitting rapid time- and wavelength-resolved femtosecond pump-probe spectroscopy. Measurements on a thin sample of bulk GaAs are performed across 58 simultaneous wavelengths. Differential probe transmission changes as small as approximately 2 x 10(-4) can be measured over a 5-ps delay scan in only approximately 3 min. This technology can be applied to a wide range of pump-probe measurements in condensed matter, chemistry, and biology.

Ultrahigh resolution OCT is demonstrated using a miniaturized micro-motor endoscope probe with adjustable beam focus. Real time image acquisition and focus adjustment are achieved with 8um transverse and 8um axial resolution.

We demonstrate methods for achieving high resolution imaging using alternate scanning techniques in optical coherence tomography and optical coherence microscopy. These techniques enable high transverse resolutions and overcome depth of field limitations. Cellular level resolutions in human tissue may be achieved.

We demonstrate compact ultrahigh resolution OCT systems for in vivo studies, with broadband light sources based on a commercially available Nd:Glass femtosecond laser and nonlinear fiber continuum generation. In vivo OCT images of hamster cheek pouch and human skin acquired at 4 frames per second and with 5.5 μm axial resolution are presented. These systems are robust, compact and portable.

Femtosecond pump-probe spectroscopy is a well-known method used to investigate ultrafast excited state dynamics in condensed matter, chemical, and biological systems. The standard technique uses a narrowband pump and continuum probe to excite the sample, and employs a spectrometer to acquire the wavelength dependent absorption saturation dynamics. This technique often requires the use of a femtosecond amplifier to achieve sufficient intensities for continuum generation and sufficient pump-probe signal magnitudes. With the development of 5 fs lasers, which can generate spectra spanning one octave, spectrally resolved pump-probe measurements can be performed without the need for amplifiers [1,2,3]. Although the pulse repetition rate from a laser oscillator is extremely high, pulse energies are low and signal levels are small. Standard CCD detectors cannot detect modulated signals and thus it is not possible to take advantage of high signal to noise measurements that are possible with high repetition rate laser sources. Here, we present a new technique that enables the parallel acquisition of pump-probe measurements for multiple wavelengths. This is made possible using a novel, two-dimensional smart pixel detector array, which was originally developed for high speed optical coherence tomography (OCT) [4,5]. Each pixel performs amplitude demodulation, and in combination with a diffraction grating, probe transmission signals can be acquired in parallel for multiple wavelengths. The smart pixel array can achieve sensitivities comparable to lock-in amplification but can perform demodulation of probe transmission signals at multiple wavelengths simultaneously, enabling time and wavelength resolved femtosecond pump-probe spectroscopy.

Ultrahigh resolution, real time OCT imaging is demonstrated using a compact femtosecond Nd:Glass laser that is spectrally broadened in a high numerical aperture single mode fiber. A reflective grating phase delay scanner enables broad bandwidth, high-speed group delay scanning. We demonstrate in vivo, ultrahigh resolution, real time OCT imaging at 1 microm center wavelength with <5 microm axial resolution in free space (<4 microm in tissue). The light source is robust, portable, and well suited for in vivo imaging studies.

Ultrahigh resolution OCT imaging is demonstrated using comp I act broadband light sources based on a commercially available Nd:Glass femtosecond laser with nonlinear fiber continuum generation. A tapered single mode fiber is used to generate broadband light centered at 1300 nm. Broadband light near 1064 nm can also be generated using a high numerical aperture single mode germanium doped fiber. These light sources enable ultrahigh resolution OCT imaging with 5-6 mum axial resolution at both 1064 nm and 1300 nm.

Real-time optically sectioned microscopy is demonstrated using an AC-sensitive detection concept realized with smart CMOS image sensor and structured light illumination by a continuously moving periodic pattern. We describe two different detection systems based on CMOS image sensors for the detection and on-chip processing of the sectioned images in real time. A region-of-interest is sampled at high frame rate. The demodulated signal delivered by the detector corresponds to the depth discriminated image of the sample. The measured FWHM of the axial response de ends on the spatial frequency of the projected grid illumination and is in the pm-range. The effect of using broadband incoherent illumination is discussed. The performance of these systems is demonstrated by imaging technical as well as biological samples.

Ultrahigh resolution OCT is used to visualize experimentally induced osteoarthritis in a rat knee model. Using a Cr4+:Forsterite laser, ultrahigh image resolutions of 5um are achieved in vivo. Progression of osteoarthritic remodeling and cartilage degeneration are quantified. The utility of OCT for the assessment of cartilage integrity is demonstrated.

A method and a microscopy imaging apparatus for generating an optically sectioned image of a specimen are provided. The method comprises the steps of:illuminating the specimen with a modulating, spatially periodic illumination pattern; imaging said specimen on a conjugate image plane; acquiring a plurality of signals at respective positions on said image plane, each signal corresponding to the incident light intensity at that position and having an oscillatory component caused by the modulation of the illumination pattern; and measuring a characteristic of the oscillatory component of each of the signals, whereby the measured characteristics when combined in their relative positions generate an optically sectioned image of the specimen.