A dual-modality probe utilizing intravascular ultrasound and optical coherence tomography for intravascular imaging applications

We have developed a dual-modality biomedical imaging probe utilizing intravascular ultrasound (IVUS) and optical coherence tomography (OCT). It consists of an OCT probe, a miniature ultrasonic transducer and a fixed mirror. The mirror was mounted at the head of the hybrid probe 45° relative to the light and the ultrasound beams to change their propagation directions. The probe was designed to be able to cover a larger area in blood vessel by IVUS and then visualize a specific point at a much finer image resolution using OCT. To demonstrate both its feasibility and potential clinical applications, we used this ultrasound-guide OCT probe to image a rabbit aorta in vitro. The results offer convincing evidence that the complementary natures of these two modalities may yield beneficial results that could not have otherwise been obtained.     

High-resolution frequency-domain second-harmonic optical coherence tomography

We used continuum generated in an 8.5 cm long fiber by a femtosecond Yb fiber laser to improve threefold the axial resolution of frequency domain second-harmonic optical coherence tomography (SH-OCT) to 12 microm. The acquisition time was shortened by more than 2 orders of magnitude compared to the time-domain SH-OCT. The system was applied to image biological tissue of fish scales, pig leg tendon, and rabbit eye sclera. Highly organized collagen fibrils can be visualized in the recorded images. Polarization dependence on the SH has been used to obtain polarization resolved images.     

High-resolution full-field optical coherence tomography with a Linnik microscope

We describe an original microscope for high-resolution optical coherence tomography applications. Our system is based on a Linnik interference microscope with high-numerical-aperture objectives. Lock-in detection of the interference signal is achieved in parallel on a CCD by use of a photoelastic birefringence modulator and full-field stroboscopic illumination with an infrared LED. Transverse cross-section (en-face, or XY) images can be obtained in real time with better than 1-microm axial (Z) resolution and 0.5-microm transverse (XY) resolution. A sensitivity of approximately 80 dB is reached at a 1-image/s acquisition rate, which allows tomography in scattering media such as biological tissues.     

Primate retina imaging with polarization-sensitive optical coherence tomography.

Polarization-sensitive optical coherence tomography (PSOCT) is applied to determine the depth-resolved polarization state of light backreflected from the eye. The birefringence of the retinal nerve fiber layer (RNFL) was observed and measured from PSOCT images recorded postmortem in a Rhesus monkey. An image-processing algorithm was developed to identify birefringent regions in acquired PSOCT retinal images and automatically determine the thickness of the RNFL. Values of the RNFL thickness determined from histology and PSOCT were compared. PSOCT may provide a new method to determine RNFL thickness and birefringence for glaucoma diagnostics.     

Multiscan time-domain optical coherence tomography for retina imaging

A versatile time-domain optical coherence tomography system is presented that can generate cross-sectional images by using either transverse priority or depth priority scanning. This is made possible by using a transmissive scanning delay line compatible with balance detection operating at a speed similar to that of the transverse scanner used to scan the beam across the target. In vivo images from the retina are generated and shown using the same system switched to either transverse or depth priority scanning regime, by using the scanning delay line either in slow or fast scanning modes, respectively. A comparative analysis of different scanning regimes depending on image size to fit different areas to be imaged is presented. Safety thresholds due to the different continuous irradiation time per transverse pixel in different scanning regimes are also considered. We present the maximum exposure level for a variety of scanning procedures, employing either A scanning (depth priority) or T scanning (transverse priority) when generating cross-sectional images, en face images, or collecting 3D volumes.     

Polarization-sensitive optical coherence tomography for imaging human atherosclerosis

Polarization-sensitive optical coherence tomography (PS-OCT) combines the advantages of OCT with image contrast enhancement, which is based on its ability to detect phase retardation and the fast-axis angle. Both PS-OCT images and histopathology have demonstrated similar features that allowed differentiation of atherosclerotic structures (i.e., plaques) from normal tissue. Moreover, the picrosirius polarization method was used to confirm PS-OCT assessment of collagen in the fibrous cap of atherosclerotic plaques, and high-frequency (40 MHz) ultrasound images were used to identify calcium in the vessel wall. Our preliminary ex vivo investigation of human aortic specimens indicated that PS-OCT might help to identify atherosclerotic lesions.     

Characterization of optical fiber imaging bundles for swept-source optical coherence tomography

Fiber imaging bundles have been investigated for use in endoscopic optical coherence tomography (OCT) systems, to obviate the requirement for scanning components within the endoscope probe section. Images have been acquired using several optical configurations, two of which are common path in design. Configurations have been selected as having potential for miniaturization and inclusion in endoscopic-type systems, since the advantages of employing imaging bundles are most clearly seen in this type of system. The various types of bundle available are described, and the properties of the leached bundles used here are discussed in detail, with reference to their effect upon the performance of OCT systems. Images are displayed from measurements made on a range of samples.     

Wide-field optical coherence tomography: imaging of biological tissues

We describe a two-dimensional optical coherence tomography technique with which we were able to obtain multiple longitudinal slices of a biological sample directly in a single Z scan. The system is based on a femtosecond Cr4+:forsterite laser and an infrared camera for wide-field imaging of the sample with a depth resolution of 5 microm. With this imaging apparatus we were able to investigate human skin and mouse ear samples and to observe the different constitutive tissues.     

Cancellation of coherent artifacts in optical coherence tomography imaging

Coherent artifacts in optical coherence tomography (OCT) images can severely degrade image quality by introducing false targets if no targets are present at the artifact locations. Coherent artifacts can also add constructively or destructively to the targets that are present at the artifact locations. This constructive or destructive interference will result in cancellation of the true targets or in display of incorrect echo amplitudes of the targets. We introduce the use of a nonlinear deconvolution algorithm, CLEAN, to cancel coherent artifacts in OCT images of extracted human teeth. The results show that CLEAN can reduce the coherent artifacts to the noise background, sharpen the air-enamel and enamel-dentin interfaces, and improve the image contrast.     

An integrated compliant balloon ultrasound catheter for intravascular strain imaging

An integrated compliant balloon ultrasound catheter was developed to allow greater deformations in strain imaging with intravascular ultrasound. A 64-element circumferential array was placed inside a compliant silicone balloon catheter to capture real-time, phase-sensitive radio frequency (RF) data during deformation experiments. Strains over 40% could be applied to normal arterial wall tissue with intracatheter pressures as low as 200 kPa (2 atm). Strain images of a hard-soft rubber phantom, thrombus, and fibrotic plaque were produced using the integrated balloon ultrasound catheter. Results show that this catheter can apply large deformations at low pressures and image various vascular pathologies ex vivo. Potentially, it can serve as a multifunctional, intravascular therapeutic device to guide angioplasty and stent deployment.     

Characterisation of scaffold architecture and tendons using optical coherence tomography and polarisation-sensitive optical coherence tomography

Scaffolds play an important role in the generation of functional tissues using tissue-engineering techniques. To generate highly organised tissue, scaffolds must have specific internal and external architectures. Here, optical coherence tomography (OCT) is exploited to characterise the architectures of various scaffolds, in particular scaffolds which have been fabricated to support the formation of uniaxially orientated collagen bundle for use in tendon tissue engineering. In parallel, a polarisation-sensitive OCT (PSOCT) has been built to assess the collagen fibre organisation in human tendon and monitor the growth of engineering tendon constructs online and non-destructively. The impact of mechanical stimuli on the modulation of tendon tissue formation and organisation was also assessed. It is shown that conventional OCT is capable of characterising scaffold architecture and the pore size, porosity or microchannel dimension can be determined quantitatively and qualitatively. PSOCT generated birefringence images of human tendon and demonstrated that low birefringence images, associated with fewer microstructural variations, correlated to the presence of scar tissue or degenerated tissue; whereas the tissue-engineered tendon exhibited lower degree of birefringence.     

Full-field optical coherence tomography with thermal light

A simple optical coherence tomography system has been developed based on a white-light Linnik interferometric microscope with its reference mirror mounted on a piezoelectric translator. The geometrical extension of the optics allows efficient illumination of this device with a low-power (3-W) light bulb, yielding full-field interferometric images at 50 Hz with a fast CCD camera. Owing to the very broad spectral width of the light source and of the camera response, we achieved axial resolutions equal to 1.1 microm in free space and 0.7 microm through a standard microscope cover plate. Tomographic images of an epithelial cell smear and of an hematological sample are shown.     

Quantitative blood speed imaging with intravascular ultrasound

Previously, we presented a method of real-time arterial color flow imaging using an intravascular ultrasound (IVUS) imaging system, where real-time RF A-scans were processed with an FIR (finite-impulse response) filter bank to estimate relative blood speed. Although qualitative flow measurements are clinically valuable, realizing the full potential of blood flow imaging requires quantitative flow speed and volume measurements in real time. Unfortunately, the rate of RF echo-to-echo decorrelation is not directly related to scatterer speed in a side-looking IVUS system because the elevational extent of the imaging slice varies with range. Consequently, flow imaging methods using any type of decorrelation processing to estimate blood speed without accounting for spatial variation of the radiation pattern will have estimation errors that prohibit accurate comparison of speed estimates from different depths. The FIR filter bank approach measures the rate of change of the ultrasound signal by estimating the slow-time spectrum of RF echoes. A filter bank of M bandpass filters is applied in parallel to estimate M components of the slow-time DFT (discrete Fourier transform). The relationship between the slow-time spectrum, aperture diffraction pattern, and scatterer speed is derived for a simplified target. Because the ultimate goal of this work is to make quantitative speed measurements, we present a method to map slow time spectral characteristics to a quantitative estimate. Results of the speed estimator are shown for a simulated circumferential catheter array insonifying blood moving uniformly past the array (i.e., plug flow) and blood moving with a parabolic profile (i.e., laminar flow)     

Compact multimodal adaptive-optics spectral-domain optical coherence tomography instrument for retinal imaging

We have developed a compact, multimodal instrument for simultaneous acquisition of en face quasi-confocal fundus images and adaptive-optics (AO) spectral-domain optical coherence tomography (SDOCT) cross-sectional images. The optical system including all AO and SDOCT components occupies a 60x60 cm breadboard that can be readily transported for clinical applications. The AO component combines a Hartmann-Shack wavefront sensor and a microelectromechanical systems-based deformable mirror to sense and correct ocular aberrations at 15 Hz with a maximum stroke of 4 microm. A broadband superluminescent diode source provides 4 mum depth resolution for SDOCT imaging. In human volunteer testing, we observed up to an 8 dB increase in OCT signal and a corresponding lateral resolution of <10 microm as a result of AO correction.     

Monte Carlo modeling of optical coherence tomography imaging through turbid media

We combine a Monte Carlo technique with Mie theory to develop a method for simulating optical coherence tomography (OCT) imaging through homogeneous turbid media. In our model the propagating light is represented by a plane wavelet; its line propagation direction and path length in the turbid medium are determined by the Monte Carlo technique, and the process of scattering by small particles is computed according to Mie theory. Incorporated into the model is the numerical phase function obtained with Mie theory. The effect of phase function on simulation is also illustrated. Based on this improved Monte Carlo technique, OCT imaging is directly simulated and phase information is recorded. Speckles, resolution, and coherence gating are discussed. The simulation results show that axial and transversal resolutions decrease as probing depth increases. Adapting a light source with a low coherence improves the resolution. The selection of an appropriate coherence length involves a trade-off between intensity and resolution.     

Interferometer for optical coherence tomography

We describe a new interferometer setup for optical coherence tomography (OCT). The interferometer is based on a fiber arrangement similar to Young's two-pinhole interference experiment with spatial coherent and temporal incoherent light. Depth gating is achieved detection of the interference signal on a linear CCD array. Therefore no reference optical delay scanning is needed. The interference signal, the modulation of the signal, the axial resolution, and the depth range are derived theoretically and compared with experiments. The dynamic range of the setup is compared with OCT sensors in the time domain. To our knowledge, the first images of porcine brain and heart tissue and human skin are presented.     

Ultrahigh-resolution full-field optical coherence tomography

We have developed a white-light interference microscope for ultrahigh-resolution full-field optical coherence tomography of biological media. The experimental setup is based on a Linnik-type interferometer illuminated by a tungsten halogen lamp. En face tomographic images are calculated by a combination of interferometric images recorded by a high-speed CCD camera. Spatial resolution of 1.8 microm x 0.9 microm (transverse x axial) is achieved owing to the extremely short coherence length of the source, the compensation of dispersion mismatch in the interferometer arms, and the use of relatively high-numerical-aperture microscope objectives. A shot-noise-limited detection sensitivity of 90 dB is obtained in an acquisition time per image of 4 s. Subcellular-level images of plant, animal, and human tissues are presented.     

Parallel optical coherence tomography system

We present the design and procedures for implementing a parallel optical coherence tomography (POCT) imaging system that can be adapted to an endoscopic format. The POCT system consists of a single mode fiber (SMF) array with multiple reduced diameter (15 microm) SMFs in the sample arm with 15 microm center spacing between fibers. The size of the array determines the size of the transverse imaging field. Electronic scanning eliminates the need for mechanically scanning in the lateral direction. Experimental image data obtained with this system show the capability for parallel axial scan acquisition with lateral resolution comparable to mechanically scanned optical coherence tomography systems.     

Time-domain optical coherence tomography with digital holographic microscopy

We show that digital holography can be combined easily with optical coherence tomography approach. Varying the reference path length is the means used to acquire a series of holograms at different depths, providing after reconstruction images of slices at different depths in the specimen thanks to the short-coherence length of light source. A metallic object, covered by a 150-microm-thick onion cell, is imaged with high resolution. Applications in ophthalmology are shown: structures of the anterior eye, the cornea, and the iris, are studied on enucleated porcine eyes. Tomographic images of the iris border close to the pupil were obtained 165 microm underneath the eye surface.     

Choroidal perfusion measurements made with optical coherence tomography

Choroidal perfusion measurements are complicated by the choroid's location posterior to the retina and its associated retinal blood vessels. Optical coherence tomography is a relatively new imaging technique with sufficient spatial resolution to isolate choroidal backscattering events from the posterior eye. We modified a speckle imaging algorithm to analyze sequential axial depth scans obtained from posterior rat eye to obtain an indicator of choroidal perfusion. This indicator is correlated with known changes in choroidal blood flow in response to increased intraocular pressure.