Hybrid fluorescence, PET, and CT for small animal imaging

493 Objectives While recent developments in instrumentation and imaging agents have enabled the use of near-infrared fluorescence (NIRF) as an alternative modality for molecular imaging (MI), quantitative fluorescence-enhanced optical tomography (FEOT) remains to be validated. By using dual-labeled NIRF and PET imaging agents, we seek to validate FEOT using conventional PET MI in a hybrid small animal PET/CT/NIRF scanner. Unfortunately, FEOT systems developed previously utilizing benchtop devices require a large footprint, and are not suitable for incorporation with commercial small animal scanners. Methods We miniaturized a time-dependent NIRF imaging system and installed it within the gantry of the Siemens Inveon dedicated PET/CT small animal scanner to enable FEOT and validation of FEOT against PET. The system consists of a CCD camera equipped with an image intensifier, a diode laser controlled by a compact single board controller, a dual-axis galvanometer to direct excitation light beam, and RF circuit modules for homodyne detection of the phase of fluorescence signals. The performance of the hybrid system was tested, characterized, and validated using a mouse-shaped solid phantom with a fluorescent inclusion. The finite element volume of the phantom was first generated from CT, and fluorescence images at several projections were collected to reconstruct a 3D distribution of the fluorophore through FEOT. Dual-labeled agents targeting primary site and lymph node metastases were also used on a tumor bearing mouse to validate the results of the FEOT against PET/CT images in a live animal. Results The results showed that the location of the fluorescent inclusion can be reconstructed accurately, and the site of the tumor with fluorescent agent obtained from the FEOT matches the location obtained from the PET/CT images. Conclusions We developed a hybrid system that could retrofit commercial small animal scanners to allow multimodal MI. Research Support This work was supported in parts by the National Institutes of Health (R01 CA135673 and U54 CA136404)