Noise statistics of phase-resolved optical coherence tomography imaging: single-and dual-beam-scan Doppler optical coherence tomography.

Noise statistics of phase-resolved optical coherence tomography (OCT) imaging are complicated and involve noises of OCT, correlation of signals, and speckles. In this paper, the statistical properties of phase shift between two OCT signals that contain additive random noises and speckle noises are presented. Experimental results obtained with a scattering tissue phantom are in good agreement with theoretical predictions. The performances of the dual-beam method and conventional single-beam method are compared. As expected, phase shift noise in the case of the dual-beam-scan method is less than that for the single-beam method when the transversal sampling step is large.

Dual-beam-scan Doppler optical coherence angiography for birefringence-artifact-free vasculature imaging.

Dual-beam-scan Doppler optical coherence angiography (DB-OCA) enables high-speed, high-sensitivity blood flow imaging. However, birefringence of biological tissues is an obstacle to vasculature imaging. Here, the influence of polarization and birefringence on DB-OCA imaging was analyzed. A DB-OCA system without birefringence artifact has been developed by introducing a Faraday rotator. The performance was confirmed in vitro using chicken muscle and in vivo using the human eye. Birefringence artifacts due to birefringent tissues were suppressed. Micro-vasculatures in the lamina cribrosa and nerve fiber layer of human eyes were visualized in vivo. High-speed and high-sensitivity micro-vasculature imaging involving birefringent tissues is available with polarization multiplexing DB-OCA.

High-penetration swept source Doppler optical coherence angiography by fully numerical phase stabilization.

A high-penetration swept-source optical coherence tomography (HP-SS-OCT) system based on a 1-µm short cavity laser is developed. Doppler OCT processing is applied, along with a custom-made numerical phase stabilization algorithm; this process does not require additional calibration hardware. Thus, our phase stabilization method is simple and can be employed in a variety of SS-OCT systems. The bidirectional blood flow and vasculature in the deep choroid was successfully imaged via two Doppler modes that use different time intervals for Doppler processing. En face projection image of squared power of Doppler shift is compared to ICGA, and the utility of our method is verified.

Variable velocity range imaging of the choroid with dual-beam optical coherence angiography.

In this study, we present dual-beam Doppler optical coherence angiography with variable beam separation. Altering beam distance, independently of the scanning protocol, provides a flexible way to select the velocity range of detectable blood flow. This system utilized a one-micrometer wavelength light source to visualize deep into the posterior eye, i.e., the choroid. Two-dimensional choroidal vasculature maps of a human subject acquired with different beam separations, and hence with several velocity ranges, are presented. Combining these maps yields a semi-quantitative visualization of axial velocity of the choroidal circulation. The proposed technique may be useful for identifying choroidal abnormalities that occur in pathological conditions of the eye.

Enhanced imaging of choroidal vasculature by high-penetration and dual-velocity optical coherence angiography.

Dual-beam-scan Doppler optical coherence angiography (DB-OCA) with a 1-µm-wavelength probe is demonstrated for improved in vivo choroidal angiograms of the human eye. This method utilizes two scanning beams with spatial and temporal separation on the retina, and provides two measurable velocity ranges. The method achieves higher sensitivity to very low velocity flows than conventional Doppler optical coherence tomography. Moreover, longer wavelengths allowing greater penetration, enhanced visualization of choroidal vessels is verified with en-face projection images of the Doppler shift squared. Specifically, better choroidal vasculature visibility is achieved at a wavelength of 1 µm than at 840 nm.

Comprehensive in vivo micro-vascular imaging of the human eye by dual-beam-scan Doppler optical coherence angiography.

Comprehensive angiography provides insight into the diagnosis of vascular-related diseases. However, complex microvascular networks of unstable in vivo organs such as the eye require micron-scale resolution in three dimensions and a high sampling rate to access a wide area as maintaining the high resolution. Here, we introduce dual-beam-scan Doppler optical coherence angiography (OCA) as a label-free comprehensive ophthalmic angiography that satisfies theses requirements. In addition to high resolution and high imaging speed, high sensitivity to motion for detecting tiny blood flow of microvessels is achieved by detecting two time-delayed signals with scanning of two probing beams separated on a sample. We present in vivo three-dimensional imaging of the microvasculature of the posterior part of the human eye. The demonstrated results show that this technique may be used for comprehensive ophthalmic angiography to evaluate the vasculature of the posterior human eye and to diagnose variety of vascular diseases.

Parabolic BM-scan technique for full range Doppler spectral domain optical coherence tomography.

A full range spectral domain optical coherence tomography (SD-OCT) technique that relies on the linear phase modulation of one of the interferometer arms has been widely utilized. Although this method is useful, the mirror image elimination is not perfect for samples in which regions with high axial motion exist. In this paper, we introduce a new modulation pattern to overcome this mirror image elimination failure. This new modulation is a parabolic phase modulation in the transverse scanning direction, and is applied to the SD-OCT reference beam by an electro-optic modulator. Flow phantom and in vivo experiments demonstrate that for moving structures with large velocities, this parabolic phase modulation technique presents better mirror image elimination than a standard linear phase modulation method. A direct consequence of this enhanced mirror image removal is an improved velocity range obtained with phase-resolved Doppler imaging. Consequently, applying the proposed technique in retinal blood flow measurements may be useful for ophthalmologic diagnosis.

Half-ball lens couples a beveled fiber probe for depth-resolved spectroscopy: Monte Carlo simulations.

In this study, we propose a beveled fiber-optic probe coupled with a half-ball lens for improving the depth-resolved fluorescence measurements of epithelial tissue. The Monte Carlo (MC) simulation results show that for a given excitation-collection fiber separation, the probe design with a bevel-angled collection fiber is more sensitive to detect fluorescence photons emitted from the shallow layer of tissue, whereas the flat-tip collection fiber is in favor of probing fluorescence photons originating from deeper tissue areas. This compact half-ball lens-beveled fiber probe design has the potential to facilitate the depth-resolved fluorescence detection of epithelial tissue.

Estimation of optical properties of turbid media: experimental comparison of spatially and temporally resolved reflectance methods.

We compare two methods for the optical characterization of turbid media. The estimates of the absorption and reduced scattering coefficients (mu(a) and mu(')(s)) by a spatially resolved method and a time-resolved method are performed on tissue-like phantoms. Aqueous suspension of microspheres and Intralipid are used as scattering media with the addition of ink as an absorber. mu(')(s) is first measured on weakly absorbing media. The robustness of these measurements is then tested with respect to a variation of mu(a). The spatially resolved method gave more accurate estimates for mu(')(s) whereas the time-resolved method gave better results for mu(a) estimates.

Beveled fiber-optic probe couples a ball lens for improving depth-resolved fluorescence measurements of layered tissue: Monte Carlo simulations.

In this study, we evaluate the feasibility of designing a beveled fiber-optic probe coupled with a ball lens for improving depth-resolved fluorescence measurements of epithelial tissue using Monte Carlo (MC) simulations. The results show that by using the probe configuration with a beveled tip collection fiber and a flat tip excitation fiber associated with a ball lens, discrimination of fluorescence signals generated in different tissue depths is achievable. In comparison with a flat-tip collection fiber, the use of a large bevel angled collection fiber enables a better differentiation between the shallow and deep tissue layers by changing the excitation-collection fiber separations. This work suggests that the beveled fiber-optic probe coupled with a ball lens has the potential to facilitate depth-resolved fluorescence measurements of epithelial tissues.

Analysis of simulated and experimental backscattered images of turbid media in linearly polarized light: estimation of the anisotropy factor.

Optical characterization of biological tissues is of real interest to improve medical diagnosis, in particular in the detection of precancerous tissues. We propose a new, noninvasive method allowing the estimation of the anisotropy factor. This method is based on the image analysis of the Q element of the Stokes vector backscattered from the turbid medium. These Q-element images show specific patterns depending on g. Therefore the use of Fourier descriptors (FDs) on simulated data to discriminate the specific geometrical features of the Q element enabled us to determine a linear relation between the anisotropy factor and six FDs. This method was applied on experimental data obtained with calibrated solutions. The anisotropy factor was estimated with a maximum relative error of 13%.

Backscattered stokes vectors of turbid media: anisotropy factor and reduced scattering coefficient estimation.

Optical characterization of biological tissues is of real interest to improve medical diagnosis and in particular in the detection of precancerous tissues. The reduced scattering coefficient micro's and the absorption coefficient microa are the most commonly retrieved coefficients. Some methods also allow to obtain the anisotropy factor g, but only few of them are non-invasive. We propose a new non-invasive method allowing the estimation of the anisotropy factor and the reduced scattering coefficient. This method is based on the image analysis of the Q-element of Stokes vector backscattered from the turbid medium. These Q-element images show specific patterns depending on g, and micro's is determined by the size of the patterns. Therefore the use of Fourier Descriptors (FD) on simulated and experimental data, to discriminate the specific geometrical features of the Q-element, enabled us to determine the anisotropy factor and the scattering coefficient.

Activity of the human visual cortex measured non-invasively by diffusing-wave spectroscopy.

Activity of the human visual cortex, elicited by steady-state flickering at 8Hz, is non-invasively probed by multi-speckle diffusingwave spectroscopy (DWS). Parallel detection of the intensity fluctuations of statistically equivalent, but independent speckles allows to resolve stimulation-induced changes in the field autocorrelation of multiply scattered light of less than 2%. In a group of 9 healthy subjects we find a faster decay of the field autocorrelation function during the stimulation periods for data measured with a long-distance probe (30mm source-receiver distance) at 2 positions over the occipital cortex (t-test: t(8) = -2.672, p = 0.028 < 0.05 for position 1, t(8) = -2.874, p = 0.021 < 0.05 for position 2). In contrast, no statistically significant change is seen when a short-distance probe (16mm source-receiver distance) is used (t-test: t(8) = -2.043, p = 0.075 > 0.05 for position 1, t(8) = -2.146, p = 0.064 > 0.05 for position 2). The enhanced dynamics observed with DWS is positively correlated with the functional increase of blood volume in the visual cortex, while the heartbeat rate is not affected by stimulation. Our results indicate that the DWS signal from the visual cortex is governed by the regional cerebral blood flow velocity.

Small-animal MRI: signal-to-noise ratio comparison at 7 and 1.5 T with multiple-animal acquisition strategies.

OBJECTIVE: The purpose of this study was to compare the signal-to-noise ratio (SNR) of phantom and rat brain images performed at 1.5 T on a clinical MR system and at 7 T on a small-animal experimental system. Comparison was carried out by taking into account SNR values based on a single sample acquisition at 1.5 and 7 T as well as on simultaneous imaging of multiple samples at 1.5 T. METHODS: SNR was experimentally assessed on a phantom and rat brains at 1.5 and 7 T using 25 mm surface coils and compared to theoretical SNR gain estimations. The feasibility of multiple-animal imaging, using the hardware capabilities available on the 1.5 T system, was demonstrated. Finally, rat brain images obtained on a single animal at 7 T and on multiple animals acquired simultaneously at 1.5 T were compared. RESULTS: Experimentally determined SNR at 7 T was far below theoretical estimations. Taking into account chemical shift, susceptibility artifacts and modifications of T1 and T2 relaxation times at higher field, a 7-T system holds limited advantage over a 1.5-T system. Instead, a multiple-animal acquisition methodology was demonstrated on a clinical 1.5-T scanner. This acquisition method significantly increases imaging efficiency and competes with single animal acquisitions at higher field. CONCLUSION: Multiple-animal imaging using a standard clinical scanner has a great potential as a high-throughput acquisition method for small animals.

Pulsation-resolved deep tissue dynamics measured with diffusing-wave spectroscopy.

We present a technique for measuring transient microscopic dynamics within deep tissue with sub-second temporal resolution, using diffusing-wave spectroscopy with gated single-photon avalanche photodiodes (APDs) combined with standard ungated multi-tau correlators. Using the temporal autocorrelation function of a reference signal allows to correct the temporal intensity autocorrelation function of the sample signal for the distortions induced by the non-constant average photon count rate. We apply this technique to pulsation-synchronized measurements of tissue dynamics in humans. Measurements on the forearm show no dependence on the pulsation phase. In contrast, the decay rate of the DWS signal measured on the wrist over the radial artery shows a pulsation-induced modulation of 60-90% consistent with pulsatile variations of arterial erythrocyte flow velocity. This might make time-resolved DWS interesting as a sensitive and fast method for investigating deep tissue perfusion, e.g. in intensive care.

Diffusing-wave spectroscopy from head-like tissue phantoms: influence of a non-scattering layer.

We investigate the influence of a non-scattering layer on the temporal field autocorrelation function of multiple scattered light from a multilayer turbid medium such as the human head. Data from Monte Carlo simulations show very good agreement with the predictions of the correlation-diffusion equation with boundary conditions taking into account non-diffusive light transport within the non-scattering layer. Field autocorrelation functions measured at the surface of a multilayer phantom including a non-scattering layer agree well with theory and simulations when the source-receiver distance is significantly larger than the depth and the thickness of the non-scattering layer. Our results show that for source-receiver distances large enough to probe the dynamics in the human cortex, the cortical diffusion coefficient obtained by analyzing field autocorrelation functions neglecting the presence of the non-scattering cerebrospinal fluid layer is underestimated by about~$40\,\%$ in situations representative of the human head.

Scattering coefficient determination in turbid media with backscattered polarized light.

A simple empirical method is presented to determine the scattering coefficient mu' s from backscattered polarized images of turbid media. It uses the ratio, pixel by pixel, of two images that are the second and the first backscattered Stokes parameter images Q and I, respectively. Taking this image ratio, then integrating it over the azimuth angle, we get a function depending on the distance from the light entrance point. This function has a maximum. Using Monte Carlo simulations, for a fixed reduced scattering coefficient mu s and for an anisotropy factor g varying between 0 and 0.8, it is found a linear relationship between the scattering coefficient mu s and the inverse of the maximum position of this function.

Geometric depolarization in patterns formed by backscattered light.

We formulate a framework to extend the idea of Berry's topological phase to multiple light scattering, and in particular to backscattering of linearly polarized light. We show that the randomization of the geometric Berry's phases in the medium leads to a loss of the polarization degree of the light, i.e., to a depolarization. We use Monte Carlo simulations in which Berry's phase is calculated for each photon path. Then we average over the distribution of the geometric phases to calculate the form of the patterns, which we compare with experimental patterns formed by backscattered light between crossed or parallel polarizers.

Description and time reduction of a Monte Carlo code to simulate propagation of polarized light through scattering media.

Propagation of polarized light through a scattering medium has been studied with a Monte Carlo code to obtain polarized backscattered images. Studies of these backscattered patterns obtained with polarized illumination can be used as a technique to characterize the medium anisotropy factor g. First we present the different steps of the Monte Carlo simulation that describe polarized light propagation in a turbid medium. Monte Carlo is a good tool to simulate the backscattered polarized light but is time-consuming. Therefore, we consider two ways to decrease the computation time. The first way deals with angle sampling of the light direction. The second takes advantage of backscattered image symmetry to divide the simulation time by a factor of 4. By combining these two techniques we significantly decrease the code computation time.