Multi-Modality Diffuse Fluorescence Imaging Applied to Preclinical Imaging in Mice

This thesis aims to explore the anatomical and functional information by developing new macroscopic multi-modality fluorescence imaging schemes. Adding anatomical imaging to functional modalities such as fluorescence enables better visualization and recovery of fluorescence images, in turn, improving the monitoring and assessment of biological parameters in tissue. Based on this motivation, fluorescence was combined with ultrasound (US) imaging first and then magnetic resonance imaging (MRI). In both cases, the systems characterization and reconstruction performance were evaluated by simulations and phantom experiments. Eventually, they were applied to in vivo molecular imaging in models of cancer and atherosclerosis in mice. Results were presented in three peer-reviewed journals, which are included in this thesis and shortly described below. A first article presented a dual-modality imaging system combining continuous-wave transmission fluorescence imaging with three dimensional (3D) US imaging. Using motorized X-Y stages, the fluorescence-US imaging system was able to collect boundary fluorescent emission, and acoustic pulse-echoes delineating the 3D surface and position of fluorescent inclusions within the sample. A validation in phantoms showed that using the US anatomical priors, the fluorescent reconstruction quality was significantly improved. Furthermore, a pilot in-vivo study using an Apo-E mouse evaluated the feasibility of this dual-modality imaging approach for future animal studies. In a second endeavor, and based on the first work, we improved the fluorescence-US imaging system in terms of sampling precision and reconstruction algorithms. Specifically, now combining US imaging and profilometry, both the fluorescent target and 3D surface of sample could be obtained in order to achieve improved fluorescence reconstruction. Furthermore, a