Optical calibration protocol for an x-ray and optical multimodality tomography system dedicated to small-animal examination.

A small-animal multimodality tomography system dedicated to the coregistration of fluorescence optical signal and x-ray measurements has been developed in our laboratory. The purpose of such a system is to offer the possibility of getting in vivo anatomical and functional information simultaneously. Moreover, anatomical measurements can be used as a regularization factor to achieve more accurate reconstructions of the biodistribution of fluorochromes and to speed up treatment. A dedicated acquisition protocol has been established, and the methodology of the reconstruction of the three-dimensional distribution of the biomarkers under cylindrical geometry consistent with classic computed tomography has been implemented. A phantom study was conducted to evaluate and to fix the parameters for the coregistration. These test experiments were reproduced by considering anesthetized mice that had thin glass tubes containing fluorochromes inserted into their esophagus. The instrument is also used for an in vivo biological study conducted on mice with lung tumors, tagged with near-infrared optical probes (targeting probes such as Transferin-AlexaFluor750).

In vivo mice lung tumor follow-up with fluorescence diffuse optical tomography.

We present in vivo experiments conducted with a new fluorescence diffuse optical tomographic (fDOT) system on cancerous mice bearing mammary murine tumors. We first briefly present this new system that has been developed and its associated reconstruction method. Its main specificity is its ability to reconstruct the fluorescence yield even in heterogeneous and highly attenuating body regions such as lungs and to enable mouse inspection without immersion in optical index matching liquid (Intralipid and ink). Some phantom experiments validate the performance of this new system for heterogeneous media inspection. Its use for a mice study is then related. It consists in the follow-up of the lungs at different stages of tumor development after injection of RAFT-(cRGD)4-Alexa700. As expected, the reconstructed fluorescence increases along with the tumor stage. These results validate the use of our system for biological studies of small animals.

Coagulation dynamics of a blood sample by multiple scattering analysis.

We report a new technique to measure coagulation dynamics on whole-blood samples. The method relies on the analysis of the speckle figure resulting from a whole-blood sample mixed with coagulation reagent and introduced in a thin chamber illuminated with a coherent light. A dynamic study of the speckle reveals a typical behavior due to coagulation. We compare our measured coagulation times to a reference method obtained in a medical laboratory.

Fluorescence diffuse optical tomography for free-space and multifluorophore studies.

We present two major advances in preclinical fluorescence-enhanced diffuse optical tomography (fDOT) system and assess its performance. It is now possible to perform experiments without adaptation liquid or a glass plate over the animal, and our system is equipped with a filter wheel in order to discriminate two injected fluorophores. Evaluation carried out on characterization phantoms and in vivo on mice demonstrates enriched use of the system for biological studies on small animals.

Bimodal ultrasound and fluorescence approach for prostate cancer diagnosis.

Finding a way to combine ultrasound and fluorescence optical imaging on an endorectal probe may improve early detection of prostate cancer. The ultrasound provides morphological information about the prostate, while the optical system detects and locates fluorophore-marked tumors. A tissue-mimicking phantom, which is representative of prostate tissues both on its optical (absorption mu(a) and diffusion mu(s) (')) and its ultrasound properties, has been made by our team. A transrectal probe adapted to fluorescence diffuse optical tomography measurements was also developed. Measurements were taken on the prostate phantom with this probe based on a pulsed laser and a time-resolved detection system. A reconstruction algorithm was then used to help locate and quantify fluorescent inclusions of different concentrations at fixed depths.

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.