A. Da Silva

Cea Leti, Grenoble, Rhône-Alpes, France

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Publications (23)6.02 Total impact

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    ABSTRACT: Fluorescence enhanced diffuse optical tomography is an emergent diagnosis tool for the localization and the quantification of fluorescent probes. This technique can be considered as a complement but sometimes could also replace the classical ionizing radiation imaging techniques, and in particular if a simple, inexpensive, non invasive and accurate instrumentation is sought. The term molecular imaging can be broadly defined as the in vivo characterization and measurement of biological processes at the cellular and molecular level. For 5 years now, the CEA-LETI has built a base of knowledge in markers and instrumentation within the framework of small animal imaging. More recently, for the purpose of a specific approach for deep tissue screening, a dedicated instrumentation has been developed for human being examination.
    Control and Automation, 2008 16th Mediterranean Conference on; 07/2008
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    ABSTRACT: This paper presents a method based on fluorescence diffuse optical tomography for reconstructing the fluorescence yield of heterogeneous and arbitrary shaped medium such as small animals. The experimental set-up is presented and the associated reconstruction method making mouse inspection without immersion in optical index matching liquid (Intralipid and ink) possible is detailed. Some phantom experiments have been carried out to characterize this new system and to validate its use for non immersed heterogeneous media and a first experiment on a mouse is presented. These results validate further use of our system for biological studies of small animals.
    Biomedical Imaging: From Nano to Macro, 2008. ISBI 2008. 5th IEEE International Symposium on; 06/2008
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    ABSTRACT: The present paper is devoted to a comparison between time- resolved fluorescence diffuse optical tomography and continuous wave fluorescence diffuse optical tomography. Both of these techniques aim at reconstructing 3D biodistribution of fluorescent markers embedded in biological tissues. The study is restricted in the time domain to the exploitation of the first three temporal moments of measurements. The temporal benefits in terms of reconstruction have been shown to depend strongly on the optical parameters of the medium investigated as well as the fluorescence lifetime.
    Biomedical Imaging: From Nano to Macro, 2008. ISBI 2008. 5th IEEE International Symposium on; 06/2008
  • Biomedical Optics; 03/2008
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    ABSTRACT: Fluorescence-enhanced diffuse optical tomography is expected to be useful to the collection of functional information from small animal models. This technique is currently limited by the extent of tissue heterogeneity and management of the shape of the animals. We propose an approach based on the reconstruction of object heterogeneity, which provides an original solution to the two problems. Three evaluation campaigns are described: the first two were performed on phantoms designed to test the reconstructions in highly heterogeneous media and noncontact geometries; the third was conducted on mice with lung tumors to test fluorescence yield reconstruction feasibility in vivo.
    Applied Optics 09/2007; 46(22):4896-906. · 1.69 Impact Factor
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    ABSTRACT: Small animal diffuse optical tomography is an appealing tool for the investigation of molecular events in cancer research and drug developments. The combination of the functional information brought by an optical system and the anatomical information delivered by X-Rays enables i) a fast multimodality animal examination; ii) the correlation between the biodistribution of the molecular probes and the morphology of the animal; iii) a more accurate optical data reconstructions by using the anatomy of the animal as a constrain in the reconstructions. A small animal multimodality tomographer for the coregistration of fluorescence optical signals and X-rays measurements is used in the present study. The optical system is composed with a CW laser and a CCD camera coupled with an appropriate combination of filters for the fluorescence detection. The animal is placed inside a transparent tube filled with an index matching fluid. The X-ray generator and detector have been positioned perpendicularly to the optical chain. Original optical calibration techniques have been developed in order to control at any time the alignment between the incident beam, the axis of the cylinder and the focus plan of the CCD. Specific developments have also been handled for obtaining the geometry correlation between optical and X-rays data reconstructions. This experimental setup is used in the present work for a study conducted on different kinds of fluorochromes for the purpose of the development of new molecular probes. The instrument is also used for in vivo biological study conducted on mice bearing tumors in the lungs, and tagged with near infrared optical probes (targeting probes such as Transferin- AlexaFluor 750 or such as RAFT-(cRGD)4-Alexa700/Alexa750).
    Proc SPIE 06/2007;
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    ABSTRACT: A fluorescence enhanced diffuse optical tomography algorithm taking into account the optical heterogeneities is presented. It is suitable for continuous wave acquisitions and naturally handles complex shaped object. Therefore, it allows in vivo studies of small animals injected with target-specific fluorescent probes without immersion fluid. A comparison with previous methods conducted on simulations is presented. A validation experiment performed on the same mouse at different stage of lung tumors growth shows the ability of the system to be used for biological studies
    Biomedical Imaging: From Nano to Macro, 2007. ISBI 2007. 4th IEEE International Symposium on; 05/2007
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    ABSTRACT: We describe a novel method for localizing a fluorescent inclusion in a homogeneous turbid medium through the use of time-resolved techniques. Based on the calculation of the mean time of the fluorescence curves, the method does not require a priori knowledge of either the fluorescence lifetime or the mean time of the instrument response function since it adopts a differential processing approach. Theoretical expressions were validated and experiments for assessing the accuracy of localization were carried out on liquid optical phantoms with a small fluorescent inclusion. The illumination and detection optical fibers were immersed in the medium to achieve infinite medium geometry as required by the model used. The experimental setup consisted of a time-correlated single-photon counting system. Submillimeter accuracy was achieved for the localization of the inclusion.
    Applied Optics 05/2007; 46(11):2131-7. · 1.69 Impact Factor
  • Proceedings of SPIE; 03/2007
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    ABSTRACT: A small animal multimodality tomographer dedicated to the co-registration of fluorescence optical signal and X-rays measurements has been developed in our laboratory. The purpose of such a system is to offer the possibility to get in vivo anatomical and functional information at once. Moreover, anatomical measurements can be used as a regularization factor in order to get the reconstructions of the biodistribution of fluorochromes more accurate and to speed up the treatment. The optical system is basically composed with a CW laser (Krypton, 752 nm) for an optimal excitation of Alexa-Fluor 750 fluorochromes, and a CCD camera coupled with a combination of filters for the fluorescence detection. The animal is placed inside a transparent tube filled with an index matching fluid. In order to perform multiple views of fluorescence data acquisitions, the cylinder is fixed to a rotating stage. The excitation beam is brought to the cylinder via two mirrors mounted on translation plates allowing a vertical scan. The optical data acquisitions are performed with a high sensitivity CCD camera. The X-ray generator and the X-ray detector have been placed perpendicularly to the optical chain. A first study on phantoms was conducted to evaluate the feasibility, to test the linearity and the reproducibility, and to fix the parameters for the co-registration. These test experiments were reproduced by considering mice in the oesophagus of which the previous tubes were inserted. Finally, the performance of the system was evaluated in vivo on mice bearing tumours in the lungs, tagged with Transferrin-AlexaFluor 750.
    Proc SPIE 03/2007;
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    ABSTRACT: A small animal multimodality tomographer dedicated to the co-registration of fluorescence optical signal and X-rays measurements has been developed in our laboratory. The purpose of such a system is to offer the possibility to get in vivo anatomical and functional information at once. Moreover, anatomical measurements can be used as a regularization factor in order to get the reconstructions of the biodistribution of fluorochromes more accurate and to speed up the treatment. The optical system is basically composed with a CW laser (Krypton, 752 nm) for an optimal excitation of Alexa-Fluor 750 fluorochromes, and a CCD camera coupled with a combination of filters for the fluorescence detection. The animal is placed inside a transparent tube filled with an index matching fluid. In order to perform multiple views of fluorescence data acquisitions, the cylinder is fixed to a rotating stage. The excitation beam is brought to the cylinder via two mirrors mounted on translation plates allowing a vertical scan. The optical data acquisitions are performed with a high sensitivity CCD camera. The X-ray generator and the X-ray detector have been placed perpendicularly to the optical chain. A first study on phantoms was conducted to evaluate the feasibility, to test the linearity and the reproducibility, and to fix the parameters for the co-registration. These test experiments were reproduced by considering mice in the oesophagus of which thin glass tubes containing fluorochromes were inserted. Finally, the performance of the system was evaluated in vivo on mice bearing tumours in the lungs, tagged with Transferin-AlexaFluor 750.
    Proc SPIE 03/2007;
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    ABSTRACT: Fluorescence enhanced diffuse optical tomography (fDOT) is envisioned to be useful to collect functional information from small animal models. For oncology applications, cancer-targeted fluorescent markers can be used as a surrogate of the cancer activity. We are developing a continuous wave fDOT bench intended to be integrated in systems dedicated to whole body small animal fluorescence analyses. The focus is currently put on the reconstruction of non immersed small animals imaged by a CCD camera. The reconstruction stage already corrects the tissue heterogeneity artifacts through the computation of an optical heterogeneity map. We will show how this formalism coupled with the determination of the animal boundaries performed by a laser scanner, can be used to manage non contact acquisitions. The time of reconstruction for a 10 × 9 laser source positions, 45 × 40 detector elements and 14 × 11 × 14 mesh voxels is typically 10 minutes on a 3GHz PCs corresponding to the acquisition time allowing the two tasks to be performed in parallel. The system is validated on an in vivo experiment performed on three healthy nude mice and a mouse bearing a lung tumor at 10, 12 and 14 days after implantation allowing the follow up of the disease. The 3D fluorescence reconstructions of this mouse are presented and the total fluorescence amounts are compared.© (2007) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
    02/2007;
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    ABSTRACT: This paper presents a new fluorescence diffuse optical tomographic (fDOT) system and its associated reconstruction method. It is able to reconstruct the fluorescence yield even in heterogeneous and highly attenuating regions. Furthermore our reconstruction method makes mouse inspection without immersion in optical index matching liquid (Intralipid and ink) possible. Some phantom experiments have been carried out to characterize this new fDOT system and to validate its use for heterogeneous media. A mice study consisting in the follow up of the lungs at different stages of tumor development is then related. These results validate the use of our system for biological studies of small animals.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 02/2007; 2007:2626-9.
  • 01/2007;
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    Nuclear Inst. and Methods in Physics Research, A. 01/2007; 571(1-2):56-59.
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    ABSTRACT: A small animal tomographer dedicated to co-registration of fluorescence optical signal and X-rays measurements is under development. An exact analytical solution to the diffusion equation used for modeling the optical forward problem has been established.
    Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment 01/2007; 571(1):118-121. · 1.14 Impact Factor
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    ABSTRACT: Numerical and analytical approaches for the forward solver used in noncontact continuous wave fluorescence optical tomography are considered. Experiments have been carried out on a half cylinder resin phantom with Alexa750 fluorophores inclusions to test the feasibility of these two approaches.
    Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment 01/2007; 571(1):203-206. · 1.14 Impact Factor
  • Journal de Radiologie 10/2006; 87(10):1530-1530. · 0.35 Impact Factor
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    ABSTRACT: A discussion on recent works on diffusive inverse problems is presented with a special focus on three-dimensional imaging methods and their application to small animal imaging by fluorescence-enhanced Diffuse Optical Tomography. A numerical approach using the Finite Element Method for handling problems modelled by elliptic coupled partial differential equations is justified by the complexity of the geometry of the system but is known to be time- and memory-consuming. The resolution of the adjoint problem considerably speeds up the treatment and allows a full 3D resolution. Nevertheless, because of the ill-posedness of the problem, the reconstruction scheme is sensitive to a priori knowledge on the parameters to be reconstructed. In this study, a multiple step, self-regularized, reconstruction algorithm for the spatial distribution of the fluorescent regions is presented. We introduce the prior knowledge of the regions of interest via a segmentation of the results performed with a first rough reconstruction of the fluorescent regions. The results are then refined along iterations of the segmentation/reconstruction scheme.© (2005) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
    04/2005;
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    ABSTRACT: A discussion on recent works on diffusive inverse problems is presented with a special focus on three-dimensional imaging methods and their application to small animal imaging by fluorescence-enhanced Diffuse Optical Tomography. A numerical approach using the Finite Element Method for handling problems modelled by elliptic coupled partial differential equations is justified by the complexity of the geometry of the system but is known to be time- and memory-consuming. The resolution of the adjoint problem considerably speeds up the treatment and allows a full 3D resolution. Nevertheless, because of the ill-posedness of the problem, the reconstruction scheme is sensitive to a priori knowledge on the parameters to be reconstructed. In this study, a multiple step, self-regularized, reconstruction algorithm for the spatial distribution of the fluorescent regions is presented. We introduce the prior knowledge of the regions of interest via a segmentation of the results performed with a first rough reconstruction of the fluorescent regions. The results are then refined along iterations of the segmentation/reconstruction scheme.
    Proc SPIE 01/2005;