A handheld fluorescence molecular tomography system for intraoperative optical imaging of tumor margins.

PURPOSE Accurate identification of tumor margins presents a major challenge in the surgical treatment of human cancers. Inability of complete removal of tumor lesions after surgery causes local recurrence and increases the incidence of developing tumor metastasis. It is clear that novel approaches that allow defining tumor margins intraoperatively for removal of small tumor lesions in the surgical cavity is critical for improving prognosis of cancer patients. To facilitate image-guided surgery using targeted optical imaging probes, we have developed a reflection-mode fluorescence molecular tomography (FMT) system with a handheld probe that is able to provide three-dimensional tumor margin information. METHODS The imaging method and system were validated using both simulated and phantom experiments. We further examined the accuracy of the handheld FMT system in an orthotopic mouse mammary tumor model following systemic delivery of near-infrared (NIR) dye-labeled and urokinase plasminogen activator receptor targeted magnet iron oxide nanoparticles. RESULTS Our results show that when the targets are located within 5 mm beneath the surface of the media, fluorescent images can be reliably detected and reconstructed with an average positional error of 0.5 mm laterally and 1.5 mm axially. For in vivo imaging in the mouse tumor model, the location and size of the tumor detected by FMT correlated well with that measured by the magnetic resonance imaging (MRI). CONCLUSIONS Our system can three-dimensionally image targets located at a depth of up to 7 mm. The in vivo results suggest that in combination with targeted optical imaging probes, this handheld FMT system can be potentially used as an intraoperative tool for the detection of tumor margins and for image-guided surgery.