Extended short wave infrared three-dimensional fluorescence and X-ray CT molecular tomography (SWIR FMT)

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Near-infrared (NIR) fluorescence imaging has been considered over the past 2 decades for biological and clinical imaging. In contrast to visible light, NIR light can penetrate tissues through several centimeters due to reduced light attenuation. To achieve quantification and three-dimensional fluorescence imaging in-vivo we have developed Fluorescence Molecular Tomography (FMT) and demonstrated readings of biological function in animals and humans using different classes of fluorescent agents. We have further developed hybrid FMT-XCT, achieved by incorporation of an X-ray Computed Tomography (XCT) system onto the same gantry as the FMT system. We showed that the hybrid system not only adds anatomical references to the fluorescence images but also achieves more accurate FMT reconstructions than stand-alone FMT, by feeding XCT information into the FMT inversion code for attenuation correction and improved regularization of the inverse problem. FMT-XCT has been employed in recent years for high resolution three-dimensional imaging of bone remodeling, lung cancer, quantification of asthmatic inflammation or characterization of rheumatoid arthritis in animals and humans. The current application proposes a next grand step into the development of the FMT technology, which is expected to bring a marked improvement in the resolution achieved, by adapting operation of the system to the so called short wave infrared window (SWIR, 1000-1700nm). The advantage of SWIR over NIR-I is that of significant reduced photon scattering, which can lead to significant improvements in the resolution achieved. While fluorescence imaging in the SWIR area has been impeded so far by the lack of sensitive cameras and biocompatible fluorescent probes suitable for this window, the recent development of promising contrast agents and camera technology has rendered SWIR region as very promising for imaging applications. Therefore, the aim of this proposal is to translate our existing FMT-XCT system into the world’s first SWIR FMT system. Two critical adaptations are required. First we must utilize Indium gallium arsenide (InGaAs) cameras, over the limited spectral response NIR-I FMT cameras used today. Second, it is important to modify the forward problem employed in image reconstruction, so that it accurately models photon propagation at reduced scatter. Then, we will validate the new SWIR FMT system by assessing its ability to pinpoint small tumors with high spatial resolution or to visualize small amounts of fluorescence-labelled cells in vivo. We expect that SWIR FMT will define a new standard in fluorescence imaging achieving resolution and accuracy that was never before available to diffuse, three-dimensional fluorescence images of tissues.