Development of an optical system for preclinical molecular imaging of atherothrombosis

Abstract : In this thesis work, we develop optical imaging protocols for the observation of then anoparticles on tissue slices in order to further link their localization and their “behaviour” to the biological pathological environment. Bimodal zinc and iron oxide-based MRI/optical nanoparticle contrast agents (Zn(Fe)O) have been synthesised with a novel azeotropicpolyol method in glycol solvents (DEG and PG). The most potent NPs, as regard to their MR contrast power, have been coated with carboxymethyl pullulan, polyethylene glycol,carboxymethyl dextran (CMD) and fucoidan, the latter being a polysaccharide able to specifically bind to the vascular wall. The coated NPs were injected into rat to locate atherothrombosis by MRI. Then the histological slices of harvested diseased tissue were imaged with our homemade optical microscope. Water removal using Dean-Stark apparatus is a novel strategy for the synthesis of NPs in polyol solution with high yield and small size.The NPs show the good magnetic and optical properties at room temperature. The coated nanoparticles were injected into an atherothrombotic rat model to locate the thrombus by MRI prior to sacrifice of the animals and tissue collection for histological study by optical microscopy. The difference of MRI images between before and after injection with Fucoidan-NPs and CMD-NPs is clear. The results indicated that fucoidan-NPs are linked to the thrombus. Some type of microscopies, such as fluorescent microscopy, dark field microscopy, hyperspectral dark field microscopy and interference dark field microscopy have been developed for the detection of NPs in liquid medium and in the histological tissue. By analyzing the spectrum of every pixel and comparing to the spectrum of reference materials, hyperspectral microscopy can detect the presence of nanomaterial on exposed tissue slices, locate, identify, and characterize them. Zn(Fe)O NPs would therefore constitute a potential bimodal contrast agent for MRI and optical imaging. Although many advance optical tools have been developed, but we found it is still a challenge to identify reliably the NPs in the tissue.
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Dinh Hoang Nguyen. Development of an optical system for preclinical molecular imaging of atherothrombosis. Imaging. Université Sorbonne Paris Cité, 2017. English. ⟨NNT : 2017USPCD062⟩. ⟨tel-02294001⟩

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