Small animal whole body radio-fluorescence tomography: a pilot study.

Objectives: Positron emission tomography (PET) and fluorescence molecular imaging or tomography (FMI or FMT) are commonly used for in vivo small animal imaging in the visualization of biological processes and events at functional or molecular levels. However, PET suffers from low resolution partly because of the physical limitation of γ detectors, while FMI is interfered by the high background noise generated from scattered excitation light and auto-fluorescence. In this study, we were aimed to develop a new small animal whole body tomographic imaging technology, named radio-fluorescence tomography (RFT), which utilized γ radiation excited fluorescence in a specially designed calcium tungstate film to achieve three-dimensional imaging of the radioactive tracer inside a small animal body.

Methods: We developed a RFT system that consisted of a high sensitive charge-couple device camera (EMCCD, Andor DU888+, UK), a radiation-to-fluorescence film, an optical filter, and a rotation platform (Figure 1a). The film was made from calcium tungstate in order to convert the γ radiation emitted from radioactive tracers into red light fluorescence, and designed as a cylindrical chamber to cover an imaging object. The EMCCD captures the fluorescent signal on the surface of the film from 360-degee. Then, the imaging object was scanned by a micro-CT system to obtain its anatomical structure. After that, a new iterative 3D reconstruction algorithm was designed to visualized the 3D bio-distribution of the radiotracer inside the object body. The RFT system was validated through a series of phantom and in vivo small animal studies by using the ¹⁸F-FDG.

Results: The preliminary results of the phantom experiment demonstrated that the RFT system can achieve very high signal-to-noise ratio (SNR > 50) with very low radioactivity (1 μCi), because the film can efficiently covert the extremely high energy γ radiation into low energy fluorescence, and there was no excitation light, hence no background scattering and auto-fluorescence. The resolution was about 1 mm, which was better than the conventional small animal PET. The in vivo results of the two tumor-bearing xenografts also proved that RFT can successfully visualize the 3D bio-distribution of the ¹⁸F-FDG in side tumor lesions (Figure 1b).

Conclusion: The RFT system can achieve small animal whole body imaging and visualize the ¹⁸F-FDG distribution in 3D. It holds great potential in providing in vivo tomographic images with better resolution and SNR than conventional PET and FMI. Research Support: This study is supported by the National Natural Science Foundation of China with grant number: 81227901, 81527805, 61231004, and 61671449.