Acousto-optic imaging of absorbing objects embedded in highly scattering media remains challenging since the detectable signal which is suitable for image reconstruction is weak. Yet, significant improvements were made possible by the joint use of (i) a newly developed and characterized high peak-power laser diode source and (ii) the Fourier Transform Acousto-Optic Imaging (FT-AOI) technique. Albeit FT-AOI was previously reported and demonstrated state-of-the-art performances in real-time imaging, the technique was nevertheless only remonstrated for low-scattering phantoms. Here, we highlight that using a 9 W high-peak power, while maintaining an average power below 1W, proved the ability of the overall setup to probe highly scattering media at video frame rate.
The assessment of materials viscoelastic properties often represents a means of diagnosis or characterization of biological tissues and biomaterials. In this paper, we introduce a new optical method for the evaluation of dynamical properties of viscoelastic media. The approach is based on time-resolved spatial speckle imaging, using a continuous wave CW illumination and a standard CCD detector. We demonstrate that an estimation of viscoelastic properties is possible, by analyzing intensity and contrast profiles of scattering spot images acquired over multiple exposure times. The accuracy of this approach is evaluated using simulated tissue mimicking media having well known optical and dynamical properties.
We developed a fluorescence imaging microscope system intended for the localization within artery slices of a gadolinium-based macromolecular biospecific magnetic resonance (MR) contrast agent used for the visualization of atherothrombosis. As the contrast agent is not initially fluorescent, we substitute some gadolinium ions for terbium ions to make them fluorescent while preserving their chemical characteristics. A long fluorescence emission time constant enables us to have a suitable signal-to-noise ratio, despite a low intensity, using pulsed illumination and time-gated imaging. Images of rat arteries show that the contrast agent is indeed localized on the specific regions of the tissues. We currently have a tool that allows us to understand and optimize the MR contrast agent.
Acousto-optic imaging (AOI) is an emerging technique in the field of biomedical optics which combines the optical
contrast allowed by diffuse optical tomography with the resolution of ultrasound (US) imaging. In this work we report
the implementation, for that purpose, of a CMOS smart-pixels sensor dedicated to the real-time analysis of speckle
patterns. We implemented a highly sensitive lock-in detection in each pixel in order to extract the tagged photons after
an appropriate in-pixel post-processing. With this system we can acquire images in scattering samples with a spatial
resolution in the 2mm range, with an integration time compatible with the dynamic of living biological tissue.
Diffuse light in tissue can be a very interesting tool for medical diagnosis, especially if one considers the fluctuations of
the speckle pattern. Of course, speckle analysis suffers from the low spatial coherence of speckle patterns, and multipixel
detection is required in order to increase the signal to noise ratio. There is therefore a need of a setup with a high
sensitivity, capable of outputting a signal from noise through averaging on a high number of pixels, as the signal can be
lower than the photon level for one image and one frame. Furthermore, such a processing has to be done at a very high
acquisition rate. “Smart-pixels” arrays can represent a major breakthrough in this field.
Diffuse Correlation Spectroscopy (DCS) is based on the temporal correlations of the speckle pattern from the light that
has diffused through a biological media. Measurements must be made on a small coherence area of the size of a speckle
grain. Summing independent measurement increases the SNR as the square root of the number of detectors. We present a
bi-dimensionnal pixel CMOS detector array specially designed for this task, with parallel in-pixel demodulation and
temporal correlations computation. Optical signals can be processed at a rate higher than 10,000 samples per second with
demodulation frequencies in the MHz range.
We have already demonstrated the potentiality of interferometry to perform timeresolved
measurements of the light scattered by a tissue: the fluctuations of the speckle
pattern, linked to a wavelength-modulation of the source, are registered, and the time-resolved
average intensity can be numerically obtained from these data[1]. The competitive results were
obtained with a simple photodiode as detector[2].
Such a method can be cheaper and more accessible for biomedical applications than
direct time-resolved methods, but it is not its unique advantage: this method allows to perform
Diffusing Wave Spectroscopy (DWS) with selected photon pathlengths[3,4]; for instance, we
have shown that we can improve the spatial resolution in transillumination imaging of a
dynamic heterogeneity through the selection of short photon transit times[4]. Therefore such a
method can offer interesting applications, for example in mammography.
A way to improve the signal to noise ratio of this method can consist in multiplying
the number of detectors. That's the reason why we decide to consider the use of a high speed
camera, that can reach a rate of 1000 frames per second. We will present the first results
obtained with this new system. The performance will be discussed, and compared to our
previous setup.
Diffusing Wave Spectroscopy (DWS) consists in the measurement of temporal correlation of the electromagnetic field in the diffusion regime, allowing a scan of dynamical properties deep inside a medium. DWS is of special interest in biomedical optics, as it is sensitive to blood circulation in capillaries inside the tissue.
However one main difficulty of this technique concerns data extraction which implies to perform an inverse problem taking into account the geometry and the optical coefficients of the medium. The use of time-resolved detection has been proved to be an efficient tool to discriminate the DWS information, but the photon path lengths were up to now limited to a few tens mean free paths.
In order to perform time-resolved DWS for much longer photon paths, we used a new method, based on the use of an interferometer and a wavelength modulated source. We have already demonstrated that this method, in addition to its lower cost, was very efficient to perform time-resolved measurements of the light scattered by a thick scattering medium. We will show in this poster some measurements performed by transillumination through a thick medium (4cm), opening the possibility of Time-Resolved DWS measurements in the human breast.
KEYWORDS: Tissue optics, Sensors, Reflectivity, Picosecond phenomena, Streak cameras, Scattering, Optical testing, In vivo imaging, Dielectric filters, Monte Carlo methods
We develop a new sensor for the local in vivo measurement of optical coefficients near the surface of a tissue. To be less sensitive to the heterogeneous surface of the sample, we decided to perform space and time-resolved measurements. The sensor is a bundle of fibres. The
excitation light is generated by a mode-locked Ti-Sa laser at 800nm and filtered by a 1.5nm bandwidth dielectric filter in order to limit group velocity dispersion in the monomode excitation fibre. The reflectance light is collected by gradient index fibres at 250μm and 1.3 mm from the source. The detection is performed with a Hamamatsu M5675 synchroscan streak camera. The whole system allows a time resolution of about 5ps. We made comparisons between time and space resolved Monte-Carlo numerical simulations and in vitro experimental data obtained with unskimmed UHT milk which is a known reference medium. The system does not rely on the absolute value of the reflected light intensity nor depend on the intensity ratio between different fibres since the distance between the medium and the fibres as well as the fibres tip cleanness cannot be guaranteed in vivo. As a consequence we use global characteristic of the time resolved curves such as the FWHM and their evolution with the distance from the source. The good agreement between the simulations and the experimental data lets us envisage to use numerically pre-computed tables for a real time determination of the local scattering mean free path and the anisotropy factor . We soon will be able to perform
measurements with biological tissues, in vitro in a first time and in vivo in a second time.
A clinical study of the evolution of the space resolved near infrared reflectance with the subcutaneous layers thickness, at rest, on the vastus lateralis, is used to determine convenient sets of muscle and fat optical coefficients at 850 nm and 780 nm. These coefficients are then used to establish pre-calculated 3 layers MC simulations tables of the reflectance as a function of the fat thickness. Real time inversion during effort is then performed to determine the absolute muscle oxygenation.
A clinical study of the evolution of the space resolved reflectance with the subcutaneous layers thickness, at rest, on the vastus lateralis, is used to determine convenient sets of muscle and fat optical coefficients at 850 nm. The results are compared to the data available in the literature. When the same study will be completed at 780 nm, these coefficients will be used in 3 layers MC simulations to establish pre-calculated tables of the reflectance as a function of the fat thickness and of the muscle absorption coefficient. The goal of this study is eventually to perform real time inversion during effort in order to determine the muscle oxygenation with this very simple technique (part 2).
We explore in this paper a new method to perform time-resolved measurements of the diffuse light transmitted through a thick turbid medium. This method is based on the analysis of the speckle fluctuations due a wavelength modulated source. A time resolution of about 50 ps is already achieved, and we expect to improve this result soon. This method could allow the design of low cost setups to perform such measurements.
We have already demonstrated that some optical coefficients of turbid media ((mu) a, (mu) s') can be derived from time and space resolved backscattered light measurements in the case of semi-infinite geometry, or multi-layered media, using the experimental results obtained far enough from the illumination area, that is where and when the diffusion approximation is valid. Our purpose is now to determine if this type of measurements can be used to explore the different moments of the scattering phase function. The same experimental set-up consisting of a titanium-sapphire pulsed laser and a streak camera was therefore used to measure the reflectance at earlier times and closer to the light source. Experiments were performed with aqueous solutions of calibrated latex microspheres. Various values of the spheres diameter were alternately used in order to vary the anisotropy factor g. Comparison with Monte-Carlo simulations were achieved for the resolution of the inverse problem. The influence of the shape of the phase function was also investigated.
Our purpose is to develop an optical technique for in-vivo and non-invasive diagnosis using backscattered light measurements. We have already demonstrated that optical coefficients of turbid media ((mu) a, (mu) s) can be derived from time and space-resolved reflectance in the case of semi-infinite geometry. This procedure was then applied to the investigation of multi-layered media: the upper layer was an aqueous solution of calibrated latex microspheres in water and the lower layer of the sample was a solid phantom. Two different types of phantoms were used. In the first set of experiments, we used an absorbing medium for under layer. In the second case, the lower layer was an absorbing and scattering phantom. Comparison with Monte-Carlo simulations were achieved for the resolution of the inverse problem.
Time and space resolved measurements of diffuse backscattered light form turbid media were performed to determinate the optical coefficients of biological tissues. The reflectance maps registered on a streak camera were analyzed with two different methods based on the diffusion approximation. These fast and practical methods were initially tested on suspensions of latex spheres in water to compare the experimental results with the theoretical coefficients derived from Mie theory. Measurements were then achieved on biological tissues.
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