Jean-Marc Dinten

Noncontact fluorescence diffuse optical tomography of heterogeneous media.

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.

Analytical method for localizing a fluorescent inclusion in a turbid medium

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.

Dual-energy x-ray absorptiometry using 2D digital radiography detector: application to bone densitometry

Dual Energy X-Rays Absorptiometry (DXA) is commonly used to separate soft tissues and bone contributions in radiographs. This decomposition leads to bone mineral density (BMD) measurement. Most clinical systems use pencil or fan collimated X-Rays beam with mono detectors or linear arrays. On these systems BMD is computed from bi-dimensional (2D) images obtained by scanning. Our objective is to take advantage of the newly available flat panels detectors and to propose a DXA approach without scanning, based on the use of cone beam X-Rays associated with a 2D detector. This approach yields bone densitometry systems with an equal X and Y resolution, a fast acquisition and a reduced risk of patient motion.Scatter in this case becomes an important issue. While scattering is insignificant on collimated systems, its level and geometrical structure may severely alter BMD measurement on cone beam systems. In our presentation an original DXA method taking into account scattering is proposed. This new approach leads to accurate BMD values.In order to evaluate the accuracy of our new approach, a phantom representative of the spine regions tissue composition (bone, fat , muscle) has been designed. The comparison between the expected theoretical and the reconstructed BMD values validates the accuracy of our method. Results on anthropomorphic spine and hip regions are also presented.

Coupling X-Ray and optical tomography systems for in vivo examination of small animals

For the purpose of the co-registration of fluorescence optical signal and X-rays measurements, a multimodality tomographer has been developed in our laboratory. Such a system brings the possibility to get, on the same bench, in vivo both anatomical and functional information. Moreover, the information on the morphology of the animal can be used as a regularization factor in order to get the reconstructions of the biodistribution of fluorochromes more accurate and to reduce the computation time. A study on homogeneous phantoms was conducted to evaluate the feasibility, to test the linearity and the reproducibility, and to fix the parameters for the co-registration. More cumbersome phantoms (sacrificed mice) have then been considered and the test experiments were reproduced. Finally, results of a study conducted in vivo on mice bearing tumors in the lungs, tagged with different types of optical probes, are presented.

Fluorescence diffuse optical tomographic system for arbitrary shaped small animals

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.

Evaluation of dual-energy radiography with a digital x-ray detector

Dual-energy imaging has been proposed as a method for producing material-specific images, thus permitting separate examination of bone and soft-tissue structures. Interesting clinical results, particularly for chest, have been presented usually for screen-film or phosphor plate detectors and with single exposure. The purpose of the paper is to investigate double exposure dual-energy with a digital X-Ray detector. The study is performed with a CCD-based large field digital X-Ray detector (Paladio detector, Apelem) installed on a remote table. Dual exposure is feasible on this detector with little registration problem because we have a very short delay (< 0.5 s) between two acquisitions. For each examination, two radiographs are acquired at two different high and low energies and with adapted X-ray tube filtrations. X-ray generator energy voltages and filtrations are optimized in order to obtain thin energy peak spectra with good spectral separation (50 keV), much better than with single exposure systems. Tissue decomposition images are estimated from both acquisitions. The decomposition process is helped by the nice spectral separation. Scatter correction, applied to the raw dual-exposure acquisitions, provides an improvement of tissue decomposition. Results are shown for a chest phantom.

From bench-top small animal diffuse optical tomography towards clinical imaging

Fluorescence enhanced diffuse optical tomography is an emergent diagnosis tool for the localization and the quantification of fluorescent probes; this technique comes as a supplement or sometimes replaces the classical ionizing radiation imaging techniques, and in particular if a simple , inexpensive, non invasive and accurate instrumentation is sought. For 4 years now, the CEA-LETI has built a base of knowledge in markers and instrumentation within the framework of small animal imaging. More recently, an instrumentation has been developed, the purpose of which is a specific approach to the examination of underlying structures, deeply embedded within the tissues, and in fine for human being screening.

In vivo fluorescence molecular optical imaging: from small animal towards clinical applications

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.

Evaluation of a segmentation-based reconstruction scheme for fluorescence-enhanced diffuse optical tomography

In the framework of Fluorescence-enhanced Diffuse Optical Tomography, a numerical approach (usually the Finite Element Method) is often required because of the complexity of the geometry of the diffusing systems studied. This approach is appropriate for handling problems modelled by elliptic coupled partial differential equations 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 the present work, a multiple step, self-regularized, reconstruction algorithm for the spatial distribution of the fluorescent regions is presented. The prior knowledge of the regions of interest is introduced via a segmentation. This one is performed on the results obtained with a first rough reconstruction. The results are then refined along iterations of the segmentation/reconstruction scheme. The technique is tested on experiments performed with a home made tomographer. A phantom study is presented.

Experimental study of time-resolved measurements on turbid media: determination of optical properties and fluorescent inclusions characterization

Among the different existing techniques in optical molecular imaging, time-domain approaches can supply information on the probe concentration or localization, in case of specific fluorescent labelling. We present an experimental validation of an analytical solution to the time-domain fluorescence diffusion equation in an infinite medium. A fitting method issued from frequency domain calculations is also presented. The instrumentation employs a pulsed laser diode as light source, optical fibres, and a photomultiplier as the detector in a time correlated single photon counting (TCSPC) system. Measurements were performed on tissue simulating phantoms containing a small fluorescent inclusion, with the fibres either imbedded deep within the volume or placed at the surface, above the inclusion. Good adequacy was found between the simulations and the within medium measurements. We also demonstrate good performances of the method to recover the fluorophore localization.