I. Alex Vitkin

Speckle variance detection of microvasculature using swept-source optical coherence tomography

We report on imaging of microcirculation by calculating the speckle variance of optical coherence tomography (OCT) structural images acquired using a Fourier domain mode-locked swept-wavelength laser. The algorithm calculates interframe speckle variance in two-dimensional and three-dimensional OCT data sets and shows little dependence to the Doppler angle ranging from 75 degrees to 90 degrees . We demonstrate in vivo detection of blood flow in vessels as small as 25 microm in diameter in a dorsal skinfold window chamber model with direct comparison with intravital fluorescence confocal microscopy. This technique can visualize vessel-size-dependent vascular shutdown and transient vascular occlusion during Visudyne photodynamic therapy and may provide opportunities for studying therapeutic effects of antivascular treatments without on exogenous contrast agent.

High speed, wide velocity dynamic range Doppler optical coherence tomography (Part I): System design, signal processing, and performance

Improvements in real-time Doppler optical coherence tomography (DOCT), acquiring up to 32 frames per second at 250 x 512 pixels per image, are reported using signal processing techniques commonly employed in Doppler ultrasound imaging. The ability to measure a wide range of flow velocities, ranging from less than 20 microm/s to more than 10 cm/s, is demonstrated using an 1.3 microm DOCT system with flow phantoms in steady and pulsatile flow conditions. Based on full implementation of a coherent demodulator, four different modes of flow visualization are demonstrated: color Doppler, velocity variance, Doppler spectrum, and power Doppler. The performance of the former two, which are computationally suitable for real-time imaging, are analyzed in detail under various signal-to-noise and frame-rate conditions. The results serve as a guideline for choosing appropriate imaging parameters for detecting in vivo blood flow.

Tissue polarimetry: concepts, challenges, applications, and outlook.

Polarimetry has a long and successful history in various forms of clear media. Driven by their biomedical potential, the use of the polarimetric approaches for biological tissue assessment has also recently received considerable attention. Specifically, polarization can be used as an effective tool to discriminate against multiply scattered light (acting as a gating mechanism) in order to enhance contrast and to improve tissue imaging resolution. Moreover, the intrinsic tissue polarimetry characteristics contain a wealth of morphological and functional information of potential biomedical importance. However, in a complex random medium-like tissue, numerous complexities due to multiple scattering and simultaneous occurrences of many scattering and polarization events present formidable challenges both in terms of accurate measurements and in terms of analysis of the tissue polarimetry signal. In order to realize the potential of the polarimetric approaches for tissue imaging and characterization/diagnosis, a number of researchers are thus pursuing innovative solutions to these challenges. In this review paper, we summarize these and other issues pertinent to the polarized light methodologies in tissues. Specifically, we discuss polarized light basics, Stokes-Muller formalism, methods of polarization measurements, polarized light modeling in turbid media, applications to tissue imaging, inverse analysis for polarimetric results quantification, applications to quantitative tissue assessment, etc.

Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation

Significant improvements are reported in the measurable velocity range and tissue motion artefact rejection of a phase-resolved optical coherence tomography and optical Doppler tomography system. Phase information derived from an in-phase and quadrature demodulator is used to estimate the mean blood flow velocity by the Kasai autocorrelation algorithm. A histogram-based velocity segmentation algorithm is used to determine block tissue movement and remove tissue motion artefacts that can be faster or slower in velocity than that of the microcirculation. The minimum detectable Doppler frequency is about 100 Hz, corresponding to a flow velocity resolution of 30 μm/s with an axial-line scanning frequency of 8.05 kHz and a mean phase change measured over eight sequential scans; the maximum detectable Doppler frequency is ±4 kHz (for bi-directional flow) before phase wrap-around.

High speed, wide velocity dynamic range Doppler optical coherence tomography (Part III): in vivo endoscopic imaging of blood flow in the rat and human gastrointestinal tracts

We previously described a fiber based Doppler optical coherence tomography system [1] capable of imaging embryo cardiac blood flow at 4~16 frames per second with wide velocity dynamic range [2]. Coupling this system to a linear scanning fiber optical catheter design that minimizes friction and vibrations, we report here the initial results of in vivo endoscopic Doppler optical coherence tomography (EDOCT) imaging in normal rat and human esophagus. Microvascular flow in blood vessels less than 100 microm diameter was detected using a combination of color-Doppler and velocity variance imaging modes, during clinical endoscopy using a mobile EDOCT system.

High speed, wide velocity dynamic range Doppler optical coherence tomography (Part II): Imaging in vivo cardiac dynamics of Xenopus laevis

We previously reported a Doppler optical coherence tomography (DOCT) system design [1] for high-speed imaging with wide velocity dynamic range (up to 28.5 dB when acquiring 8 frames per second), operating at 1.3 m with a coherence length of 13.5 m. Using a developmental biology model (Xenopus laevis), here we test the DOCT systems ability to image cardiac dynamics in an embryo in vivo, with a simple hand-held scanner at 4 ~ 16 frames per second. In particular, we show that high fidelity DOCT movies can be obtained by increasing the reference arm scanning rate (~8 kHz). Utilizing a combination of four display modes (B-mode, color-Doppler, velocity variance, and Doppler spectrum), we show that DOCT can detect changes in velocity distribution during heart cycles, measure the velocity gradient in the embryo, and distinguish blood flow Doppler signal from heart wall motions.

Mueller matrix decomposition for extraction of individual polarization parameters from complex turbid media exhibiting multiple scattering, optical activity, and linear birefringence.

Linear birefringence and optical activity are two common optical polarization effects present in biological tissue, and determination of these properties has useful biomedical applications. However, measurement and unique interpretation of these parameters in tissue is hindered by strong multiple scattering effects and by the fact that these and other polarization effects are often present simultaneously. We have investigated the efficacy of a Mueller matrix decomposition methodology to extract the individual intrinsic polarimetry characteristics (linear retardance delta and optical rotation psi, in particular) from a multiply scattering medium exhibiting simultaneous linear birefringence and optical activity. In the experimental studies, a photoelastic modulation polarimeter was used to record Mueller matrices from polyacrylamide phantoms having strain-induced birefringence, sucrose-induced optical activity, and polystyrene microspheres-induced scattering. Decomposition of the Mueller matrices recorded in the forward detection geometry from these phantoms with controlled polarization properties yielded reasonable estimates for delta and psi parameters. The confounding effects of scattering, the propagation path of multiple scattered photons, and detection geometry on the estimated values for delta and psi were further investigated using polarization-sensitive Monte Carlo simulations. The results show that in the forward detection geometry, the effects of scattering induced linear retardance and diattenuation are weak, and the decomposition of the Mueller matrix can retrieve the intrinsic values for delta and psi with reasonable accuracy. The ability of this approach to extract the individual intrinsic polarimetry characteristics should prove valuable in diagnostic photomedicine, for example, in quantifying the small optical rotations due to the presence of glucose in tissue and for monitoring changes in tissue birefringence as a signature of tissue abnormality.

Endoscopic Doppler optical coherence tomography in the human GI tract: initial experience

BACKGROUND Expanding the current endoscopic optical coherence tomography (OCT) system with Doppler capability may augment this novel high-resolution cross-sectional imaging technique with functional blood flow information. The aim of this feasibility study was to assess the clinical feasibility of an endoscopic Doppler OCT (EDOCT) system in the human GI tract. METHODS During routine endoscopy, 22 patients were imaged by using a prototype EDOCT system, which provided color-Doppler and velocity-variance images of mucosal and submucosal blood flow at one frame per second, simultaneously with high-spatial-resolution (10-25 mum) images of tissue microstructure. The images were acquired from normal GI tract and pathologic tissues. OBSERVATIONS Subsurface microstructure and microcirculation images of normal and pathologic GI tissues, including Barretts esophagus, esophageal varices, portal hypertensive gastropathy, gastric antral vascular ectasia, gastric lymphoma, and duodenal adenocarcinoma, were obtained from 72 individual sites in vivo. Differences in vessel diameter, distribution, density, and blood-flow velocity were observed among the GI tissue pathologies imaged. CONCLUSIONS To our knowledge, this is the first study to demonstrate the feasibility of EDOCT imaging in the human GI tract during routine endoscopy procedures. EDOCT may detect the different microcirculation patterns exhibited by normal and diseased tissues, which may be useful for diagnostic imaging and treatment monitoring.

Optical and acoustic properties at 1064 nm of polyvinyl chloride-plastisol for use as a tissue phantom in biomedical optoacoustics

A novel optoacoustic phantom made of polyvinyl chloride-plastisol (PVCP) for optoacoustic studies is described. The optical and acoustic properties of PVCP were measured. Titanium dioxide (TiO2) powder and black plastic colour (BPC) were used to introduce scattering and absorption, respectively, in the phantoms. The optical absorption coefficient (mua) at 1064 nm was determined using an optoacoustic method, while diffuse reflectance measurements were used to obtain the optical reduced scattering coefficient (mus). These optical properties were calculated to be mua = (12.818 +/- 0.001)ABPC cm(-1) and mus = (2.6 +/- 0.2)S(TiO2) + (1.4 +/- 0.1) cm(-1), where ABPC is the BPC per cent volume concentration, and S(TiO2) is the TiO2 volume concentration (mg mL(-1)). The speed of sound in PVCP was measured to be (1.40 +/- 0.02) x 10(3) m s(-1) using the pulse echo transmit receive method, with an acoustic attenuation of (0.56 +/- 1.01) f(1.51+/-0.06)MHz (dB cm(-1)) in the frequency range of 0.61-1.25 MHz, and a density, calculated by measuring the displacement of water, of 1.00 +/- 0.04 g cm(-3). The speed of sound and density of PVCP are similar to tissue, and together with the user-adjustable optical properties, make this material well suited for developing tissue-equivalent phantoms for biomedical optoacoustics.

Characterization and real-time optical measurements of the ionizing radiation dose response for a new radiochromic medium

A new radiochromic film, GafChromic EBT, was investigated for use in a real-time radiation dosimetry system. It was found to be approximately eight times more sensitive to ionizing radiation dose, exhibited less postexposure development and achieved stable readout faster than one of its predecessors, GafChromic MD-55. A clear distinction in change in optical density between exposure and postexposure was observed, but the measurements obtained during exposure were not linear with time or dose. This could not be explained by a shift in wavelength of maximum change in absorbance, as it was stable at approximately 636 nm during the entire exposure range (up to 9.52 Gy). Increasing the spectral window of interest over which calculations were performed did little to correct the nonlinearity. The radiochromic film exhibited small dose rate dependence in real-time measurements, with an increase in standard deviation of change in optical density measurements from 0.9% to 1.8% over a sixfold variation in dose rate. Overall, GafChromic EBT has increased sensitivity and decreased postexposure darkening, and this bodes well for its potential role as a radiation dosimeter, including real-time applications.