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

近红外（NIR）荧光成像在过去的二十年中被认为是生物和临床成像。与可见光相比，由于光衰减减少，近红外光可以穿透组织几厘米。为了在体内实现定量和三维荧光成像，我们开发了荧光分子断层扫描（FMT），并使用不同种类的荧光剂演示了动物和人类的生物功能读数。我们进一步开发了混合FMT-XCT，通过将x射线计算机断层扫描（XCT）系统整合到与FMT系统相同的龙门上实现。我们发现，混合系统不仅在荧光图像中加入了解剖参考，而且通过将XCT信息输入到FMT反演代码中进行衰减校正和改进反问题的正则化，比单独的FMT重建更准确。近年来，FMT-XCT已被用于动物和人类骨重塑、肺癌、哮喘炎症定量或类风湿关节炎表征的高分辨率三维成像。目前的应用为FMT技术的发展提出了一个重大的下一步，通过使系统适应所谓的短波红外窗口（SWIR, 1000-1700nm）的操作，有望带来分辨率的显着提高。相对于NIR-I， SWIR的优点是光子散射显著减少，这可以显著提高分辨率。由于缺乏灵敏的相机和适合该窗口的生物相容性荧光探针，迄今为止，SWIR区域的荧光成像受到阻碍，但最近有前途的造影剂和相机技术的发展使得SWIR区域的成像应用非常有前景。因此，本提案的目的是将我们现有的FMT- xct系统转化为世界上第一个SWIR FMT系统。需要进行两个关键的调整。首先，我们必须利用铟镓砷（InGaAs）相机，在有限的光谱响应NIR-I FMT相机今天使用。其次，修改图像重建中使用的正演问题，使其准确地模拟光子在减少散射下的传播。然后，我们将通过评估其在高空间分辨率下精确定位小肿瘤或在体内观察少量荧光标记细胞的能力来验证新的SWIR FMT系统。我们期望SWIR FMT将定义荧光成像的新标准，实现以前从未有过的漫射、三维组织荧光图像的分辨率和准确性。

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.