Two-dimensional birefringence imaging in biological tissue by polarization-sensitive optical coherence tomography

Using a low-coherence Michelson interferometer, we measure two-dimensional images of optical birefringence in bovine tendon as a function of depth. Polarization-sensitive detection of the signal formed by interference of backscattered light from the sample and a mirror in the reference arm give the optical phase delay between light that is propagating along the fast and slow axes of the birefringent tendon. Images showing the change in birefringence in response to laser irradiation are presented. The technique permits rapid noncontact investigation of tissue structural properties through two-dimensional imaging of birefringence.     

Birefringence characterization of biological tissue by use of optical coherence tomography

An improved polarization-sensitive optical coherence tomography (OCT) system is developed and used to measure birefringence in porcine myocardium tissue and produce two-dimensional birefringence mapping of the tissue. Signal-to-noise issues that cause systematic measurement errors are analyzed to determine the regime in which such measurements are accurate. The advantage of polarization-sensitive OCT systems over standard OCT systems in avoiding image artifacts caused by birefringence is also demonstrated.     

Two-dimensional depth-resolved Mueller matrix characterization of biological tissue by optical coherence tomography

We built a polarization-sensitive optical coherence tomographic system and measured the two-dimensional depth-resolved full 4 x 4 Mueller matrix of biological tissue for what is believed to be the first time. The Mueller matrix measurements, which we made by varying the polarization states of the light source and the detector, yielded a complete characterization of the polarization property of the tissue sample. The initial experimental results indicated that this new approach reveals some tissue structures that are not perceptible in standard optical coherence tomography.     

Quantum optical coherence tomography of a biological sample

Quantum optical coherence tomography (QOCT) makes use of an entangled-photon light source to carry out dispersion-immune axial optical sectioning. We present the first experimental QOCT images of a biological sample: an onion-skin tissue coated with gold nanoparticles. 3D images are presented in the form of 2D sections of different orientations. In the context of quantum information, this represents the first experiment in which a quantum-entangled entity interacts with a biological specimen, generating a collection of quantum interferograms, from which an image is constructed.     

Two-dimensional depth-resolved Mueller matrix of biological tissue measured with double-beam polarization-sensitive optical coherence tomography

A double-beam polarization-sensitive system based on optical coherence tomography was built to measure the Mueller matrix of scattering biological tissue with high spatial resolution. The Jones matrix of a sample can be determined with a single scan and subsequently converted into an equivalent nondepolarizing Mueller matrix. As a result, the system can be used to measure the Mueller matrix of an unstable sample, such as soft tissue. The polarization parameters of a porcine tendon, including magnitude and orientation of birefringence and diattenuation, were extracted by decomposition of the measured Mueller matrix.     

Continuous optical coherence tomography monitoring of nanoparticles accumulation in biological tissues

In this study, dynamics of nanoparticles penetrating and accumulating in biotissue (healthy skin) was investigated in vivo by the noninvasive method of optical coherence tomography (OCT). Gold nanoshells and titanium dioxide nanoparticles were studied. The processes of the nanoparticles penetration and accumulation in biotissue are accompanied by the changes in optical properties of skin which affect the OCT images. The continuous OCT monitoring of the process of the nanoparticles penetration into skin showed that these changes appeared in 30 min after application of nanoparticles on the surface; the time of accumulation of maximal nanoparticles concentration in skin was observed in period of 1.5–3 h after application. Numerical processing of the OCT signal exhibited the increase in contrast between upper and lower parts of dermis and contrast decay of the hair follicle border during 60–150 min. The transmission electron microscopy technique confirmed accumulation of the both types of nanoparticles in biotissue. The novelty of this study is presentation of OCT ability to in vivo monitor dynamics of nanoparticles penetration and their re-distribution within living tissues.     

Quantifying tissue microvasculature with speckle variance optical coherence tomography

In this Letter, we demonstrate high resolution, three-dimensional optical imaging of in vivo blood vessel networks using speckle variance optical coherence tomography, and the quantification of these images through the development of biologically relevant metrics using image processing and segmentation techniques. Extracted three-dimensional metrics include vascular density, vessel tortuosity, vascular network fractal dimension, and tissue vascularity. We demonstrate the ability of this quantitative imaging approach to characterize normal and tumor vascular networks in a preclinical animal model and the potential for quantitative, longitudinal vascular treatment response monitoring.     

Tracking optical coherence tomography

An experimental tracking optical coherence tomography (OCT) system has been clinically tested. The prototype instrument uses a secondary sensing beam and steering mirrors to compensate for eye motion with a closed-loop bandwidth of 1 kHz and tracking accuracy, to within less than the OCT beam diameter. The retinal tracker improved image registration accuracy to <1 transverse pixel (<60 microm). Composite OCT images averaged over multiple scans and visits show a sharp fine structure limited only by transverse pixel size. As the resolution of clinical OCT systems improves, the capability to reproducibly map complex structures in the living eye at high resolution will lead to improved understanding of disease processes and improved sensitivity and specificity of diagnostic procedures.     

Second-harmonic optical coherence tomography

Second-harmonic optical coherence tomography, which uses coherence gating of second-order nonlinear optical responses of biological tissues for imaging, is described and demonstrated. Femtosecond laser pulses were used to excite second-harmonic waves from collagen harvested from rat tail tendon and a reference non-linear crystal. Second-harmonic interference fringe signals were detected and used for image construction. Because of the strong dependence of second-harmonic generation on molecular and tissue structures, this technique imparts contrast and resolution enhancement to conventional optical coherence tomography.     

Fiber-optic-bundle-based optical coherence tomography

A fiber-optic-bundle-based optical coherence tomography (OCT) probe method is presented. The experimental results demonstrate this multimode optical fiber-bundle-based OCT system can achieve a lateral resolution of 12 microm and an axial resolution of 10 microm with a superluminescent diode source. This novel OCT imaging approach eliminates any moving parts in the probe and has a primary advantage for use in extremely compact and safe OCT endoscopes for imaging internal organs and great potential to be combined with confocal endoscopic microscopy.     

Spectroscopic optical coherence tomography

Spectroscopic optical coherence tomography (OCT), an extension of conventional OCT, is demonstrated for performing cross-sectional tomographic and spectroscopic imaging. Information on the spectral content of backscattered light is obtained by detection and processing of the interferometric OCT signal. This method allows the spectrum of backscattered light to be measured over the entire available optical bandwidth simultaneously in a single measurement. Specific spectral features can be extracted by use of digital signal processing without changing the measurement apparatus. An ultrabroadband femtosecond Ti:Al(2)O(3) laser was used to achieve spectroscopic imaging over the wavelength range from 650 to 1000 nm in a simple model as well as in vivo in the Xenopus laevis (African frog) tadpole. Multidimensional spectroscopic data are displayed by use of a novel hue-saturation false-color mapping.     

Two-wavelength optical coherence tomography

We present the results of studies of the basic principles and describe the design of a low-coherence two-wavelength interferometer based on polarization-maintaining fiber. The interferometer was developed for optical coherence tomography (OCT) imaging of the internal structure of living biological tissue simultaneously at two wavelengths, 830 and 1300 nm. Images of several sites of living biological tissue are presented and analyzed.     

Holoscopy--holographic optical coherence tomography

Scanning optical coherence tomography (OCT) is limited in sensitivity and resolution by the restricted focal depth of the confocal detection scheme. Holoscopy, a combination of holography and Fourier-domain full-field OCT, is proposed as a way to detect photons from all depths of a sample volume simultaneously with uniform sensitivity and lateral resolution, even at high NAs. By using the scalar diffraction theory, as frequently applied in digital holographic imaging, we fully reconstruct the object field with depth-invariant imaging quality. In vivo imaging of human skin is demonstrated with an image quality comparable to conventionally scanned OCT.     

Imaging of human breast tissue using polarization sensitive optical coherence tomography

We report a study on the use of polarization sensitive optical coherence tomography (PSOCT) for discriminating malignant (invasive ductal carcinoma), benign (fibroadenoma) and normal (adipocytes) breast tissue sites. The results show that while conventional OCT, that utilizes only the intensity of light back-scattered from tissue microstructures, is able to discriminate breast tissues as normal (adipocytes) and abnormal (malignant and benign) tissues, PS-OCT helps in discriminating between malignant and benign tissue sites also. The estimated values of birefringence obtained from the PSOCT imaging show that benign breast tissue samples have significantly higher birefringence as compared to the malignant tissue samples.     

Combined Raman spectroscopy and optical coherence tomography device for tissue characterization

We report a dual-modal device capable of sequential acquisition of Raman spectroscopy (RS) and optical coherence tomography (OCT) along a common optical axis. The device enhances application of both RS and OCT by precisely guiding RS acquisition with OCT images while also compensating for the lack of molecular specificity in OCT with the biochemical specificity of RS. We characterize the system performance and demonstrate the capability to identify structurally ambiguous features within an OCT image with RS in a scattering phantom, guide acquisition of RS from a localized malignancy in ex vivo breast tissue, and perform in vivo tissue analysis of a scab.     

Molecularly sensitive optical coherence tomography

Molecular contrast in optical coherence tomography (OCT) is demonstrated by use of coherent anti-Stokes Raman scattering (CARS) for molecular sensitivity. Femtosecond laser pulses are focused into a sample by use of a low-numerical-aperture lens to generate CARS photons, and the backreflected CARS signal is interferometrically measured. With the chemical selectivity provided by CARS and the advanced imaging capabilities of OCT, this technique may be useful for molecular contrast imaging in biological tissues. CARS can be generated and interferometrically measured over at least 600 microm of the depth of field of a low-numerical-aperture objective.     

Optical-fiber-based Mueller optical coherence tomography

An optical-fiber-based multichannel polarization-sensitive Mueller optical coherence tomography (OCT) system was built to acquire the Jones or Mueller matrix of a scattering medium, such as biological tissue. For the first time to our knowledge, fiber-based polarization-sensitive OCT was dynamically calibrated to eliminate the polarization distortion caused by the single-mode optical fiber in the sample arm, thereby overcoming a key technical impediment to the application of optical fibers in this technology. The round-trip Jones matrix of the sampling fiber was acquired from the reflecting surface of the sample for each depth scan (A scan) with our OCT system. A new rigorous algorithm was then used to retrieve the calibrated polarization properties of the sample. This algorithm was validated with experimental data. The skin of a rat was imaged with this fiber-based system.     

Thermal-light full-field optical coherence tomography

We have built a high-resolution optical coherence tomography (OCT) system, based on a Linnik-type interference microscope, illuminated by a white-light thermal lamp. The extremely short coherence length of the illumination source and the large aperture of the objectives permit resolution close to 1 microm in three dimensions. A parallel detection scheme with a CCD camera provides cross-section (x-y) image acquisition without scanning at a rate of up to 50 Hz. To our knowledge, our system has the highest resolution demonstrated to date for OCT imaging. With identical resolution in three dimensions, realistic volume rendering of structures inside biological tissues is possible.     

Time-gated Fourier-domain optical coherence tomography

A novel optical coherence tomography (OCT) system is presented that combines Fourier-domain OCT with incoherent nonlinear time gating. By processing backscattered light in the optical domain, the user can select a restricted depth field of view for improved contrast and acquisition speed. This technique has the additional advantage that imaging is done in the infrared (approximately 1280 nm) but is detected in the visible(approximately 504 nm).     

Self-referenced Doppler optical coherence tomography

Doppler optical coherence tomography (DOCT) allows simultaneous micrometer-scale resolution cross-sectional imaging of tissue structure and blood flow. We demonstrate a fiber-optic polarization-diversity-based differential phase contrast DOCT system as a method to perform self-referenced velocimetry in highly scattering media. Using this strategy, we reduced common-mode interferometer noise to <1 Hz and improved Doppler estimates in a scattering flow phantom by a factor of 5.