Depth-resolved monitoring of glucose diffusion in tissues by using optical coherence tomography

We demonstrate the capability of the optical coherence tomography (OCT) technique for depth-resolved monitoring and quantifying of glucose diffusion in fibrous tissues (sclera). The depth-resolved and average permeability coefficients of glucose were calculated. We found that the glucose diffusion rate is not uniform throughout the tissue and is increased from approximately 2.39+/-0.73 x 10(-6) cm/s at the epithelial side to 8.63+/-0.27 x 10(-6) cm/s close to the endothelial side of the sclera. Results demonstrated that the OCT technique is capable of depth-resolved monitoring and quantification of glucose diffusion in sclera with a resolution of approximately 40 mum.     

Quadrature fringes wide-field optical coherence tomography and its applications to biological tissues

We propose and demonstrate quadrature fringes wide-field optical coherence tomography (QF WF OCT) to expand an optical Hilbert transformation to two-dimensions. This OCT simultaneously measures two quadrature interference images using a single InGaAs CCD camera to obtain en face OCT images. The axial and lateral resolutions are measured at 29 μm in air and 70 μm limited by a pixel size of camera using a superluminescent diode with a wavelength of 1.3 μm as the light source; the system sensitivity is determined to be −90 dB. The area of the en face OCT images is 4.0 mm × 4.0 mm (160 × 160  pixels). The OCT images are measured axially with steps of 10 μm. The en face OCT images of a in vivo human fingertip and a in situ rat brain are three-dimensionally measured up to the depth of about 3 mm with some degradations of a lateral resolution.     

High-resolution ultrasound-modulated optical tomography in biological tissues

We present a novel implementation of high-resolution ultrasound-modulated optical tomography that, based on optical contrast, can image several millimeters deep into soft biological tissues. A long-cavity confocal Fabry-Perot interferometer, which provides a large etendue and a short response time, was used to detect the ultrasound-modulated coherent light that traversed the scattering biological tissue. Using 15-MHz ultrasound, we imaged with high-contrast light-absorbing structures placed >3 mm below the surface of chicken breast tissue. The resolution along the axial and the lateral directions with respect to the ultrasound propagation direction was better than 70 and 120 microm, respectively. The resolution can be scaled down further by use of higher ultrasound frequencies. This technology is complementary to other imaging technologies, such as confocal microscopy and optical-coherence tomography, and has the potential for broad biomedical applications.     

Continuous focus tracking for real-time optical coherence tomography

We report an approach to achieving continuous focus tracking and a depth-independent transverse resolution for real-time optical coherence tomography (OCT) imaging. Continuous real-time focus tracking is permitted by use of a lateral-priority image acquisition sequence in which the depth-scanning rate is equivalent to the imaging frame rate. Real-time OCT imaging with continuous focus tracking is performed at 1 frame/s by reciprocal translation of a rapid lateral-scanning miniature imaging probe (e.g., an endoscope). The optical path length in the reference arm is scanned synchronously to ensure that the coherence gate coincides with the imaging beam focus. The image quality improvement is experimentally demonstrated by imaging a tissue phantom embedded with polystyrene microspheres and rabbit esophageal tissues.     

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.     

Cross-polarized backscatter in optical coherence tomography of biological tissue

We have observed that cross-polarized backscatter measured by optical coherence tomography of human skin in vivo is surprisingly strong. We identify and give evidence of its main origins: single scattering from nonspherical particles and multiple scattering by particles with sizes much larger than a wavelength. Our findings show that depolarized light scattered by dense large-diameter particles maintains a high degree of temporal coherence and that differential-polarization imaging improves contrast between particles of different sizes.     

Noninvasive monitoring of glucose concentration with optical coherence tomography

We have proposed a tested in tissue phantoms and in vivo a novel sensor based on optical coherence tomography (OCT) for noninvasive and continuous monitoring of blood glucose concentration. OCT images were obtained from pig and rabbit skin before and after glucose administration. Slopes of OCT signals decreased substantially (~40% in tissues in vivo) and linearly with the increase of blood glucose concentration from 4 to 30 mM, typical for normal and diabetic subjects. Phantom studies demonstrated 1% accuracy of scattering-coefficient measurement. Our theoretical and experimental studies suggest that glucose concentration can potentially be measured noninvasively with high sensitivity and accuracy with OCT systems.     

Real-time monitoring of structural vibration using spectral-domain optical coherence tomography

We report in this paper the development of a spectral-domain optical coherence vibration tomography (OCVT) using a broadband CCD-based spectrometer and a short-coherence white light source. We demonstrate that both the vibration amplitude and frequency can be quantified, in the frequency range 0-250 Hz, with an axial resolution of 1 μm. Furthermore, the inner structure (layer thickness) of a vibrating sample can also be quantified simultaneously. The developed OCVT is non-contact and noninvasive in nature, thus is ideal for real time and in situ monitoring of low-frequency micro-vibrations that have critical impacts on many high-precision manufacturing and engineering processes.     

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.     

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.     

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.     

Feasibility of glucose monitoring based on Brownian dynamics in time-domain optical coherence tomography

Our purpose is to investigate the feasibility of Brownian motion in time-domain optical coherence tomography (OCT) incorporated with wavelet power spectrum to monitor glucose concentration in Intralipid solution. The results show that the standard deviation (SD) of frequency in the superficial layer of single scattering region, linearly proportional to Brownian diffusion coefficient, is independent of the depth. Our preliminary results demonstrate that average SD of frequency in the single scattering region is inversely proportional to the glucose concentration in Intralipid solution, since the Brownian diffusion coefficient is a function of concentration. Thus the average SD of frequency in OCT signal is capable of differentiating the glucose concentration.     

Quantification of molecular diffusion in arterial tissues with optical coherence tomography and fluorescence microscopy

Alternations in vascular permeability for different molecules, drugs, and contrast agents might be a significant early marker of development of various diseases such as atherosclerosis. However, up to date experimental studies of molecular diffusion across vascular wall have been limited. Recently, we demonstrated that the Optical Coherence Tomography (OCT) technique could be applied for noninvasive and nondestructive quantification of molecular diffusion in different biological tissues. However, the viability of the OCT-based assessment of molecular diffusion should be validated with established methods. This study focused on comparing molecular diffusion rates in vascular tissues measured with OCT and standard fluorescent microscopy. Noninvasive quantification of tetramethylrhodamine (fluorescent dye) permeability in porcine vascular tissues was performed using a fiber-based OCT system. Concurrently, standard histological examination of dye diffusion was performed and quantified with fluorescent microscopy. The permeability of tetramethylrhodamine was found to be (2.08 ± 0.31) × 10^?5 cm/s with the fluorescent technique (n = 8), and (2.45 ± 0.46) × 10^?5 cm/s with the OCT (n = 3). Good correlation between permeability rates measured by OCT and histology was demonstrated, suggesting that the OCT-based method could be used for accurate, nondestructive assessment of molecular diffusion in multilayered tissues.     

Polarization-sensitive full-field optical coherence tomography

We present a polarization-sensitive full-field optical coherence tomography system that can produce high-resolution images of the linear retardance and reflectivity properties of biological media. En face images can be delivered at a frame rate of 3.5 Hz by combination of interferometric images acquired by two CCD cameras in an interference microscope illuminated with a tungsten halogen lamp. Isotropic spatial resolution of approximately 1.0 microm is achieved. The technique is demonstrated on ex vivo muscle tissues.